sickle cell disease

Sickle Cell Disease 

Definition

Sickle cell disease describes a group of inherited blood disorders characterized by chronic anemia, painful events, and various complications due to associated tissue and organ damage.

Because sickle cell diseases are characterized by the rapid loss of red blood cells as they enter the circulation, they are classified as hemolytic disorders, "hemolytic" referring to the destruction of the cell membrane of red blood cells resulting in the release of hemoglobin.

Description

The most common and best-known type of sickle cell disease is sickle cell anemia, which is also called meniscocytosis, sicklemia, or SS disease. All types of sickle cell disease are caused by a genetic change in hemoglobin, the oxygen-carrying protein inside the red blood cells. The red blood cells of affected individuals contain a predominance of a structural variant of the usual adult hemoglobin. This variant hemoglobin, called sickle hemoglobin, has a tendency to polymerize into rod-like structures that alter the shape of the usually flexible red blood cells. The cells take on a shape that resembles the curved blade of the sickle, an agricultural tool. Sickle cells have a shorter life span than normally shaped red blood cells. This results in chronic anemia characterized by low levels of hemoglobin and decreased numbers of red blood cells. Sickle cells are also less flexible and stickier than normal red blood cells, and can become trapped in small blood vessels preventing blood flow. This compromises the delivery of oxygen, which can result in pain and damage to associated tissues and organs. Sickle cell disease presents with marked variability, even within families.

Carriers of the sickle cell gene are said to have sickle cell trait. Unlike sickle cell disease, sickle cell trait does not cause health problems. In fact, sickle cell trait is protective against malaria, a disease caused by blood-borne parasites transmitted through mosquito bites. According to a widely accepted theory, the genetic mutation associated with the sickle cell trait occurred thousands of years ago. Coincidentally, this mutation increased the likelihood that carriers would survive malaria infection. Survivors then passed the mutation on to their offspring, and the trait became established throughout areas where malaria was common. As populations migrated, so did the sickle cell trait. Today, approximately one in 12 African Americans has sickle cell trait.

Worldwide, it has been estimated that one in every 250,000 babies is born annually with sickle cell disease. Sickle cell disease primarily affects people of African, Mediterranean, Middle Eastern, and Asian Indian ancestry. In the United States, sickle cell disease is most often seen in African Americans, in whom the disease occurs in one out of every 400 births. The disease has been described in individuals from several different ethnic backgrounds and is also seen with increased frequency in Latino Americans—particularly those of Caribbean, Central American, and South American ancestry. Approximately one in every 1000-1400 Latino births are affected.

Causes and symptoms

Humans normally make several types of the oxygen-carrying protein hemoglobin. An individual's stage in development determines whether he or she makes primarily embryonic, fetal, or adult hemoglobins. All types of hemoglobin are made of three components: heme, alpha (or alpha-like) globin, and beta (or beta-like) globin. Sickle hemoglobin is the result of a genetic change in the beta globin component of normal adult hemoglobin. The beta globin gene is located on chromosome 11. The sickle cell form of the beta globin gene results from the substitution of a single DNA nucleotide, or genetic building-block. The change from adenine to thymine at codon (position) 6 of the beta globin gene leads to insertion of the amino acid valine-instead of glutamic acid—at this same position in the beta globin protein. As a result of this change, sickle hemoglobin has unique properties in comparison to the usual type of adult hemoglobin.

Most individuals have two normal copies of the beta globin gene, which make normal beta globin that is incorporated into adult hemoglobin. Individuals who have sickle cell trait (called sickle cell carriers) have one normal beta globin gene and one sickle cell gene. These individuals make both the usual adult hemoglobin and sickle hemoglobin in roughly equal proportions, so they do not experience any health problems as a result of having the trait. Although traces of blood in the urine and difficulty in concentrating the urine can occur, neither represents a significant health problem as a result of sickle cell trait. Of the millions of people with sickle cell trait worldwide, a small handful of individuals have experienced acute symptoms. In these very rare cases, individuals were subject to very severe physical strain.

When both members of a couple are carriers of sickle cell trait, there is a 25% chance in each pregnancy for the baby to inherit two sickle cell genes and have sickle cell anemia, or SS disease. Correspondingly, there is a 50% chance the baby will have sickle cell trait and a 25% chance that the baby will have the usual type of hemoglobin. Other types of sickle cell disease include SC disease, SD disease, and S/beta thalassemia. These conditions are caused by the co-inheritance of the sickle cell gene and another altered beta globin gene. For example, one parent may have sickle cell trait and the other parent may have hemoglobin C trait (another hemoglobin trait that does not cause health problems). For this couple, there would be a 25% chance of SC disease in each pregnancy.

Normal adult hemoglobin transports oxygen from the lungs to tissues throughout the body. Sickle hemoglobin can also transport oxygen. However, once the oxygen is released, sickle hemoglobin tends to polymerize (line-up) into rigid rods that alter the shape of the red blood cell. Sickling of the red blood cell can be triggered by low oxygen, such as occurs in organs with slow blood flow. It can also be triggered by cold temperatures and dehydration.

Sickle cells have a decreased life span in comparison to normal red blood cells. Normal red blood cells survive for approximately 120 days in the bloodstream; sickle cells last only 10-12 days. As a result, the bloodstream is chronically short of red blood cells and hemoglobin, and the affected individual develops anemia.

Sickle cells can create other complications. Due to their shape, they do not fit well through small blood vessels. As an aggravating factor, the outside surfaces of sickle cells may have altered chemical properties that increase the cells' 'stickiness'. These sticky sickle cells are more likely to adhere to the inside surfaces of small blood vessels, as well as to other blood cells. As a result of the sickle cells' shape and stickiness, blockages form in small blood vessels. Such blockages prevent oxygenated blood from reaching areas where it is needed, causing pain as well as organ and tissue damage.

The severity of symptoms cannot be predicted based solely on the genetic inheritance. Some individuals with sickle cell disease develop health- or life-threatening problems in infancy, but others may have only mild symptoms throughout their lives. Individuals may experience varying degrees of health at different stages in the life cycle. For the most part, this clinical variability is unpredictable, and the reasons for the observed variability can not usually be determined. However, certain types of sickle cell disease (i.e. SC disease) tend to result in fewer and less severe symptoms on average than other types of sickle cell disease (i.e. SS disease). Some additional modifying factors are known. For example, elevated levels of fetal hemoglobin in a child or adult can decrease the quantity and severity of some symptoms and complications. Fetal hemoglobin is a normally occurring hemoglobin that usually decreases from over 90% of the total hemoglobin to under 1% during the first year of life. This change is genetically determined, although some individuals may experience elevated levels of fetal hemoglobin due to variation in the genes that control fetal hemoglobin production. Such individuals often experience a reduction in their symptoms and complications due to the ability of fetal hemoglobin to prevent the polymerization of sickle hemoglobin, which leads to sickling of the red blood cell.

There are several symptoms that warrant immediate medical attention, including the following:

• signs of infection (fever greater than >101°F or 38.3°C, coughs frequently or breathing trouble, unusual crankiness, feeding difficulties)
• signs of severe anemia (pale skin or lips, yellowing of the skin or eyes, very tired, very weak)
• signs indicating possible dehydration (vomiting, diarrhea, fewer wet diapers)

• other signs (pain or swelling in the abdomen, swollen hands or feet, screams when touched)

These can be signs of various complications that occur in sickle cell disease.

Infections and effects on the spleen

Children with sickle cell disease who are under age three are particularly prone to life-threatening bacterial infections. Streptococcus pneumoniae is the most common offending bacteria, and invasive infection from this organism leads to death in 15% of cases. The spleen, an organ that helps to fight bacterial infections, is particularly vulnerable to the effects of sickling. Sickle cells can impede blood flow through the spleen, causing organ damage, which usually results in loss of spleen function by late childhood. The spleen can also become enlarged due to blockages and/or increased activity of the spleen. Rapid enlargement of the spleen may be a sign of another complication called splenic sequestration, which occurs mostly in young children and can be life-threatening. Widespread sickling in the spleen prevents adequate blood flow from the organ, removing increasing volumes of blood from the circulation and leading to accompanying signs of severe anemia.

Painful events

Painful events, also known as vaso-occlusive events, are a hallmark symptom of sickle cell disease. The frequency and duration of the pain can vary tremendously from person to person and over an individual's life cycle. Painful events are the most common cause of hospitalizations in sickle cell disease. However, only a small portion of individuals with sickle cell disease experience frequent and severe painful events. Most painful events can be managed at home. Pain results when small blood vessel blockages prevent oxygen from reaching tissues. Pain can affect any area of the body, although the extremities, chest, abdomen, and bones are frequently affected sites. There is some evidence that cold temperatures or infection can trigger a painful event, but most events occur for unknown reasons. The hand-foot syndrome, or dactylitis, is a particular type of painful event. Most common in toddlers, dactylitis results in pain and swelling in the hands and feet, sometimes accompanied by a fever.

Anemia

Sickle cells have a high turnover rate leading to a deficit of red blood cells in the bloodstream. Common symptoms of anemia include fatigue, paleness, and a shortness of breath. A particularly severe form of anemia—aplastic anemia—occurs following infection with parvovirus. Parvovirus causes extensive destruction of the bone marrow, bringing production of new red blood cells to a halt. Bone marrow production resumes after seven to 10 days; however, given the short lives of sickle cells, even a brief shut-down in red blood cell production can cause a rapid decline in hemoglobin concentrations.

Delayed growth

The energy demands of the bone marrow for red blood cell production compete with the demands of a growing body. Children with sickle cell anemia may have delayed growth and reach puberty at a later age than normal. By early adulthood, they catch up on growth and attain normal height; however, weight typically remains below average.

Stroke

Children with sickle cell disease have a significantly elevated risk of having a stroke, which can be one of the most concerning complications of sickle cell disease. Approximately 11% of individuals with sickle cell disease will have a recognizable stroke by the age of 20. Magnetic resonance imaging studies have found that 17% of children with sickle cell anemia have evidence of a previous stroke or clinically 'silent' stroke-like events called transient ischemic events. Stroke in sickle cell disease is usually caused by a blockage of a blood vessel, but about one fourth of the time may be caused by a hemorrhage (or rupture) of a blood vessel.

Strokes result in compromised delivery of oxygen to an area of the brain. The consequences of stroke can range from life-threatening, to severe physical or cognitive impairments, to apparent or subtle learning disabilities, to undetectable effects. Common stroke symptoms include weakness or numbness that affects one side of the body, sudden behavioral changes, loss of vision, confusion, loss of speech or the ability to understand spoken words, dizziness, headache, seizures, vomiting, or even coma.

Approximately two-thirds of the children who have a stroke will have at least one more. Transfusions have been shown to decrease the incidence of a second stroke. A recent study showed that children at highest risk to experience a first stroke were 10 times more likely to stroke if untreated when compared to high-risk children treated with chronic blood transfusion therapy. High-risk children were identified using transcranial doppler ultrasound technology to detect individuals with increased blood flow speeds due to constricted intracranial blood vessels.

As of 2003, researchers are investigating various techniques for helping children with memory loss related to strokes caused by sickle cell disease.

Acute chest syndrome

Acute chest syndrome (ACS) is a leading cause of death for individuals with sickle cell disease, and recurrent attacks can lead to permanent lung damage. Therefore rapid diagnosis and treatment is of great importance. ACS can occur at any age and is similar but distinct from pneumonia. Affected persons may experience fever, cough, chest pain, and shortness of breath. ACS seems to have multiple causes including infection, sickling in the small blood vessels of the lungs, fat embolisms to the lungs, or a combination of factors.

Priapism

Males with sickle cell anemia may experience priapism, a condition characterized by a persistent and painful erection of the penis. Due to blood vessel blockage by sickle cells, blood is trapped in the tissue of the penis. Priapism may be short in duration or it may be prolonged. Priapism can be triggered by low oxygen (hypoxemia), alcohol consumption, or sexual intercourse. Since priapism can be extremely painful and result in damage to this tissue causing impotence, rapid treatment is essential.

Kidney disease

The environment in the kidney is particularly prone to damage from sickle cells. Signs of kidney damage can include blood in the urine, incontinence, and enlarged kidneys. Adults with sickle cell disease often experience insufficient functioning of the kidneys, which can progress to kidney failure in a small percentage of adults with sickle cell disease.

Jaundice and gallstones

Jaundice is indicated by a yellow tone in the skin and eyes, and alone it is not a health concern. Jaundice may occur if bilirubin levels increase, which can occur with high levels of red blood cell destruction. Bilirubin is the final product of hemoglobin degradation, and is typically removed from the bloodstream by the liver. Therefore, jaundice can also be a sign of a poorly functioning liver, which may also be evidenced by an enlarged liver. Increased bilirubin also leads to increased chance for gallstones in children with sickle cell disease. Treatment, which may include removal of the gall bladder, may be selected if the gallstones start causing symptoms.

Retinopathy

The blood vessels that supply oxygen to the retina—the tissue at the back of the eye—may be blocked by sickle cells, leading to a condition called retinopathy. This is one of the only complications that is actually more common in SC disease as compared to SS disease. Retinopathy can be identified through regular ophthalmology evaluations and effectively treated in order to avoid damage to vision.

Joint problems

Avascular necrosis of the hip and shoulder joints, in which bone damage occurs due to compromised blood flow due to sickling, can occur later in childhood. This complication can affect an individual's physical abilities and result in substantial pain.

Diagnosis

Inheritance of sickle cell disease or trait cannot be prevented, but it may be predicted. Screening is recommended for individuals in high-risk populations. In the United States, African Americans and Latino Americans have the highest risk of having the disease or trait. Sickle cell is also common among individuals of Mediterranean, Middle Eastern, and Eastern Indian descent.

A complete blood count (CBC) will describe several aspects of an individual's blood cells. A person with sickle cell disease will have a lower than normal hemoglobin level, together with other characteristic red blood cell abnormalities. A hemoglobin electrophoresis is a test that can help identify the types and quantities of hemoglobin made by an individual. This test uses an electric field applied across a slab of gellike material. Hemoglobins migrate through this gel at various rates and to specific locations, depending on their size, shape, and electrical charge. Although sickle hemoglobin (Hb S) and regular adult hemoglobin (called Hb A) differ by only one amino acid, they can be clearly separated using hemoglobin electrophoresis. Isoelectric focusing and high-performance liquid chromatography (HPLC) use similar principles to separate hemoglobins and can be used instead of or in various combinations with hemoglobin electrophoresis to determine the types of hemoglobin present.

Another test called the sickledex can help confirm the presence of sickle hemoglobin, although this test cannot provide accurate or reliable diagnosis when used alone. When Hb S is present, but there is an absence or only a trace of Hb A, sickle cell anemia is a likely diagnosis. Additional beta globin DNA testing, which looks directly at the beta globin gene, can be performed to help confirm the diagnosis and establish the exact genetic type of sickle cell disease. CBC and hemoglobin electrophoresis are also typically used to diagnose sickle cell trait and various other types of beta globin traits.

Diagnosis of sickle cell disease can occur under various circumstances. If an individual has symptoms that are suggestive of this diagnosis, the above-described screening tests can be performed followed by DNA testing, if indicated. Screening at birth using HPLC or a related technique offers the opportunity for early intervention. More than 40 states include sickle cell screening as part of the usual battery of blood tests done for newborns. This allows for early identification and treatment. Hemoglobin trait screening is recommended for any individual of a high-risk ethnic background who may be considering having children. When both members of a couple are found to have sickle cell trait, or other related hemoglobin traits, they can receive genetic counseling regarding the risk of sickle cell disease in their future children and various testing options.

Sickle cell disease can be identified before birth through the use of prenatal diagnosis. Chorionic villus sampling (CVS) can be offered as early as 10 weeks of pregnancy and involves removing a sample of the placenta made by the baby and testing the cells. CVS carries a risk of causing a miscarriage that is between one-half to one percent.

Amniocentesis is generally offered between 15 and 22 weeks of pregnancy, but can sometimes be offered earlier. Two to three tablespoons of the fluid surrounding the baby is removed. This fluid contains fetal cells that can be tested. This test carries a risk of causing a miscarriage, which is not greater than one percent. Pregnant woman and couples may choose prenatal testing in order to prepare for the birth of a baby that may have sickle cell disease. Alternately, knowing the diagnosis during pregnancy allows for the option of pregnancy termination.

Preimplantation genetic diagnosis (PGD) is a relatively new technique that involves in-vitro fertilization followed by genetic testing of one cell from each developing embryo. Only the embryos unaffected by sickle cell disease are transferred back into the uterus. PGD is currently available on a research basis only, and is relatively expensive.

Treatment

There are several practices intended to prevent some of the symptoms and complications of sickle cell disease. These include preventative antibiotics, good hydration, immunizations, and access to comprehensive care. Maintaining good health through adequate nutrition, avoiding stresses and infection, and getting proper rest is also important. Following these guidelines is intended to improve the health of individuals with sickle cell disease.

Penicillin

Infants are typically started on a course of penicillin that extends from infancy to age six. Use of this antibiotic is meant to ward off potentially fatal infections. Infections at any age are treated aggressively with antibiotics. Vaccines for common infections, such as pneumococcal pneumonia, are also recommended.

Pain management

Pain is one of the primary symptoms of sickle cell anemia, and controlling it is an important concern. The methods necessary for pain control are based on individual factors. Some people can gain adequate pain control through over-the-counter oral painkillers (analgesics). Other individuals, or painful events, may require stronger methods that can include administration of narcotics. Alternative therapies may be useful in avoiding or controlling pain, including relaxation, hydration, avoiding extremes of temperature, and the application of local warmth.

Blood transfusions

Blood transfusions are not usually given on a regular basis but are used to treat individuals with frequent and severe painful events, severe anemia, and other emergencies. In some cases blood transfusions are given as a preventative measure, for example to treat spleen enlargement or prevent a second stroke (or a first stroke in an individual shown to be at high risk).

Regular blood transfusions have the potential to decrease formation of hemoglobin S, and reduce associated symptoms. However, there are limitations and risks associated with regular blood transfusions, including the risk of blood-borne infection and sensitization to proteins in the transfused blood that can make future transfusions very difficult. Most importantly, chronic blood transfusions can lead to iron overload. The body tends to store excess iron, such as that received through transfusions, in various organs. Over time, this iron storage can cause damage to various tissues and organs, such as the heart and endocrine organs.

Some of this damage can be prevented by the administration of a medication called desferoxamine that helps the body to eliminate excess iron through the urine. Alternately, some individuals receive a new, non-standard treatment called erythrocytapheresis. This involves the automated removal of sickle cells and is used in conjunction with a reduced number of regular transfusions. This treatment helps to reduce iron overload.

Hydroxyurea

Emphasis is being placed on developing drugs that treat sickle cell anemia directly. The most promising of these drugs in the late 1990s is hydroxyurea, a drug that was originally designed for anticancer treatment. Hydroxyurea has been shown to reduce the frequency of painful crises and acute chest syndrome in adults, and to lessen the need for blood transfusions. Hydroxyurea seems to work by inducing a higher production of fetal hemoglobin. The major side effects of the drug include decreased production of platelets, red blood cells, and certain white blood cells. The effects of long-term hydroxyurea treatment are unknown; however, a nine-year follow-up study of 299 adults with frequent painful crises reported in 2003 that taking hydroxyurea was associated with a 40% reduction in mortality.

Bone marrow transplantation

Bone marrow transplantation has been shown to cure sickle cell anemia in some cases. This treatment is reserved primarily for severely affected children with a healthy donor whose marrow proteins match those of the recipient, namely a brother or sister who has inherited the same tissue type. Indications for a bone marrow transplant are stroke, recurrent acute chest syndrome, and chronic unrelieved pain.

Bone marrow transplantations tend to be the most successful in children; adults have a higher rate of transplant rejection and other complications. There is approximately a 10% fatality rate associated with bone marrow transplants done for sickle cell disease. Survivors face potential long-term complications, such as chronic graft-versus-host disease (an immunemediated attack by the donor marrow against the recipient's tissues), infertility, and development of some forms of cancer. A relatively recent advance in transplantation involves the use of donor stem cells obtained from cord blood, the blood from the placenta that is otherwise discarded following the birth of a new baby. Cord blood cells, as opposed to fully mature bone marrow cells, appear to be less likely to result in graft-versus-host disease in the recipient. This increases the safety and efficacy of the transplant procedure.

Surgery

Certain surgical interventions are utilized in the treatment of specific sickle cell-related complications. Removal of a dysfunctioning gallbladder or spleen can often lead to improvements in health. Investigations are currently underway to establish the efficacy of hip coring surgery, in which a portion of affected bone is removed to treat avascular necrosis of the hip. The hope is that this may provide an effective treatment to alleviate some pain and restore function in the affected hip.

Gene research

Replacing the gene that produces the defective hemoglobin in sickle cell disease patients with one that makes normal hemoglobin may be a possible treatment due to recent research. According to a 1998 report in Science, researchers studied the blood cells from people who carry the sickle cell gene. By using an enzyme called a ribosome, the study was able to alter sickle cells into normal cells. The ribosome cut out the mutated instructions in the cells' genetic pattern and replaced them with the correct instructions. Researchers hope that this will allow the cells to make normal hemoglobin—leading to the ultimate treatment for those with sickle cell disease.

In late 2001, genetic scientists reported that they had designed a gene that might lead to a future treatment of sickle cell anemia. Although the gene had not been tested in humans, early results showed that the injected gene protected cells from sickling. As of 2003,

Key terms

Amino acid — Organic compounds that form the building blocks of protein. There are 20 types of amino acids (eight are "essential amino acids" which the body cannot make and must therefore be obtained from food).

Anemia — A blood condition in which the level of hemoglobin or the number of red blood cells falls below normal values. Common symptoms include paleness, fatigue, and shortness of breath.

Bilirubin — A yellow pigment that is the end result of hemoglobin breakdown. This pigment is metabolized in the liver and excreted from the body through the bile. Bloodstream levels are normally low; however, extensive red cell destruction leads to excessive bilirubin formation and jaundice.

Bone marrow — A spongy tissue located in the hollow centers of certain bones, such as the skull and hip bones. Bone marrow is the site of blood cell generation.

Bone marrow transplantation — A medical procedure used to treat some diseases that arise from defective blood cell formation in the bone marrow. Healthy bone marrow is extracted from a donor to replace the marrow in an ailing individual. Proteins on the surface of bone marrow cells must be identical or very closely matched between a donor and the recipient.

Globin — One of the component protein molecules found in hemoglobin. Normal adult hemoglobin has a pair each of alpha-globin and beta-globin molecules.

Heme — The iron-containing molecule in hemoglobin that serves as the site for oxygen binding.

Hemoglobin — Protein-iron compound in the blood that carries oxygen to the cells and carries carbon dioxide away from the cells.

Hemoglobin A — Normal adult hemoglobin that contains a heme molecule, two alpha-globin molecules, and two beta-globin molecules.

Hemoglobin electrophoresis — A laboratory test that separates molecules based on their size, shape, or electrical charge.

Hemoglobin S — Hemoglobin produced in association with the sickle cell trait; the beta-globin molecules of hemoglobin S are defective.

Hemolytic — Referring to the destruction of the cell membranes of red blood cells, resulting in the release of hemoglobin from the damaged cell.

Hydroxyurea — A drug that has been shown to induce production of fetal hemoglobin. Fetal hemoglobin has a pair of gamma-globin molecules in place of the typical beta-globins of adult hemoglobin. Higher-than-normal levels of fetal hemoglobin can prevent sickling from occurring.

Impotence — The inability to have a penile erection, which can be due to tissue damage resulting from sickling within the penis (priapism).

Iron overload — A side effect of frequent blood transfusions in which the body accumulates abnormally high levels of iron. Iron deposits can form in organs, particularly the heart, and cause life-threatening damage.

Jaundice — Yellowing of the skin or eyes due to excess of bilirubin in the blood.

Magnetic resonance imaging (MRI) — A technique that employs magnetic fields and radio waves to create detailed images of internal body structures and organs, including the brain.

Meniscocytosis — Another word for sickle cell disease.

Mutation — A permanent change in the genetic material that may alter a trait or characteristic of an individual, or manifest as disease, and can be transmitted to offspring.

Narcotics — Strong, prescription medication that can be effective in treating pain, but have the potential to be habit-forming if their use is not supervised correctly.

Nucleic acid — The cellular molecules DNA and RNA that act as coded instructions for the production of proteins and are copied for transmission of inherited traits.

Ophthalmology — The medical specialty of vision and the eye.

Placenta — The organ responsible for oxygen and nutrition exchange between a pregnant mother and her developing baby.

Red blood cell — Hemoglobin-containing blood cells that transport oxygen from the lungs to tissues. In the tissues, the red blood cells exchange their oxygen for carbon dioxide, which is brought back to the lungs to be exhaled.

Screening — Process through which carriers of a trait may be identified within a population.

Sickle cell — A red blood cell that has assumed an elongated shape due to the presence of hemoglobin S.

experiments in gene therapy for sickle cell disease have been carried out in mice, using lentiviral vectors to transfer the corrective gene into the mouse's stem cells. This technique, however, has not yet been attempted in human subjects as of late 2003.

Psychosocial support

As in any lifelong, chronic disease, comprehensive care is important. Assistance with the emotional, social, family-planning, economic, vocational, and other consequences of sickle cell disease can enable affected individuals to better access and benefit from their medical care.

Prognosis

Sickle cell disease is characteristically variable between and within affected individuals. Predicting the course of the disorder based solely on genes is not possible. Several factors aside from genetic inheritance determine the prognosis for affected individuals, including the frequency, severity, and nature of specific complications in any given individual. The availability and access of comprehensive medical care also plays an important role in preventing and treating serious, acute complications, which cause the majority of sickle cell-related deaths. For those individuals who do not experience such acute events, life expectancy is probably substantially greater than the average for all people with sickle cell disease. The impact of recent medical advances supports the hypothesis that current life expectancies may be significantly greater than those estimated in the early 1990s. At that time, individuals with SS disease lived to the early- to mid-40s, and those with SC disease lived into the upper 50s on average. As of 2003, the life expectancy of persons with SS is over 50. With early detection and comprehensive medical care, most people with sickle cell disease are in fairly good health most of the time. Most individuals can be expected to live well into adulthood, enjoying an improved quality of life including the ability to choose a variety of education, career, and family-planning options for themselves.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Anemias Caused by Excessive Hemolysis: Sickle Cell Diseases." Section 11, Chapter 127 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Pregnancy Complicated by Disease: Hemoglobinopathies." Section 18, Chapter 251 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.

Periodicals

Davies, S. C., and A. Gilmore. "The Role of Hydroxyurea in the Management of Sickle Cell Disease." Blood Reviews 17 (June 2003): 99-109.

Egbert Maikler, Virginia, et al. "Children's and Adolescents' Use of Diaries for Sickle Cell Pain." Journal of the Society of Pediatric Nurses 6, no. 4 (October—December 2001): 161-169.

Harris, Leslie. "Living Well with Sickle Cell." Essence September 1999: 58.

Nienhuis,A. W., H. Hanawa, N. Sawai, et al. "Development of Gene Therapy for Hemoglobin Disorders." Annals of the New York Academy of Science 996 (May 2003): 101-111.

Seppa, N. "Gene Therapy for Sickle-cell Disease?" Science News 160, no. 24 (December 15, 2001): 372.

Steinberg, M. H., F. Barton, O. Castro, et al. "Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits up to 9 Years of Treatment." Journal of the American Medical Association 289 (April 2, 2003): 1645-1651.

Winrow, N., and E. R. Melhem. "Sickle Cell Disease and Stroke in a Pediatric Population. Evidence-Based Diagnostic Evaluation." Neuroimaging Clinics of North America 13 (May 2003): 185-196.

Yerys, B. E., D. A. White, C. F. Salorio, et al. "Memory Strategy Training in Children with Cerebral Infarcts Related to Sickle Cell Disease." Journal of Pediatric Hematology and Oncology 25 (June 2003): 495-498.

Organizations

Mayo Foundation for Medical Education and Research. http://www.mayohealth.org.

Sickle Cell Disease Association of America. 200 Corporate Point, Suite 495, Culver City, CA 90230-7633. (310) 216-6363. (800) 421-8453. 〈http://sicklecelldisease.org/〉.

Sickle Cell Disease Program, Division of Blood Diseases and Resources. National Heart, Lung, and Blood Institute. II Rockledge Centre, 6701 Rockledge Dr. MSC 7950, Bethesda, MD 20892-7950. (301) 435-0055.

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disease /dis·ease/ (dĭ-zēz´) any deviation from or interruption of the normal structure or function of any body part, organ, or system that is manifested by a characteristic set of symptoms and signs and whose etiology, pathology, and prognosis may be known or unknown. See also entries under syndrome.

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acquired cystic disease of kidney  the development of cysts in the formerly noncystic failing kidney in end-stage renal disease.

Addison's disease  bronzelike pigmentation of the skin, severe prostration, progressive anemia, low blood pressure, diarrhea, and digestive disturbance, due to adrenal hypofunction.

Albers-Schönberg disease  osteopetrosis.

allogeneic disease  graft-versus-host reaction occurring in immunosuppressed animals receiving injections of allogeneic lymphocytes.

Alpers' disease  a rare disease of young children, characterized by neuronal deterioration of the cerebral cortex and elsewhere, progressive mental deterioration, motor disturbances, seizures, and early death.

alpha chain disease  heavy chain disease characterized by plasma cell infiltration of the lamina propria of the small intestine resulting in malabsorption with diarrhea, abdominal pain, and weight loss, possibly accompanied by pulmonary involvement.

Alzheimer's disease  progressive degenerative disease of the brain, of unknown cause; characterized by diffuse atrophy throughout the cerebral cortex with distinctive histopathological changes.

Andersen's disease  glycogen storage d., type IV.

apatite deposition disease  a connective tissue disorder marked by deposition of hydroxyapatite crystals in one or more joints or bursae.

Aran-Duchenne disease  spinal muscular atrophy.

arteriosclerotic cardiovascular disease  (ASCVD) atherosclerotic involvement of arteries to the heart and to other organs, resulting in debility or death; sometimes used specifically for ischemic heart disease.

arteriosclerotic heart disease  (ASHD) ischemic heart d.

autoimmune disease  any of a group of disorders in which tissue injury is associated with humoral or cell-mediated responses to the body's own constituents; they may be systemic or organ-specific.

Ayerza's disease  polycythemia vera with chronic cyanosis, dyspnea, bronchitis, bronchiectasis, hepatosplenomegaly, bone marrow hyperplasia, and pulmonary artery sclerosis.

Banti's disease  congestive splenomegaly.

Barlow disease  scurvy in infants.

Barraquer's disease  partial lipodystrophy.

Basedow's disease  Graves' d.

Batten disease , Batten-Mayou disease

1. Vogt-Spielmeyer d.

2. more generally, any or all of the group of disorders constituting neuronal ceroid lipofuscinosis.

Bayle's disease  general paresis.

Bazin's disease  erythema induratum.

Bekhterev's (Bechterew's) disease  ankylosing spondylitis.

Benson's disease  asteroid hyalosis.

Berger's disease  IgA glomerulonephritis.

Bernhardt's disease , Bernhardt-Roth disease meralgia paresthetica.

Besnier-Boeck disease  sarcoidosis.

Best's disease  congenital macular degeneration.

Bielschowsky-Janský disease  Janský-Bielschowsky d.

Binswanger's disease  a degenerative dementia of presenile onset caused by demyelination of the subcortical white matter of the brain.

black disease  a fatal disease of sheep, and sometimes of humans, in the United States and Australia, due to Clostridium novyi, marked by necrotic areas in the liver.

Blocq's disease  astasia-abasia.

Blount disease  tibia vara.

Boeck's disease  sarcoidosis.

Bornholm disease  epidemic pleurodynia.

Bowen's disease  a squamous cell carcinoma in situ, often due to prolonged exposure to arsenic; usually occurring on sun-exposed areas of skin. The corresponding lesion on the glans penis is termed erythroplasia of Queyrat.

Brill's disease  Brill-Zinsser d.

Brill-Symmers disease  giant follicular lymphoma.

Brill-Zinsser disease  mild recrudescence of epidemic typhus years after the initial infection, because Rickettsia prowazekii has persisted in body tissue in an inactive state, with humans as the reservoir.

broad beta disease  familial dysbetalipoproteinemia; named for the electrophoretic mobility of the abnormal chylomicron and very-low-density lipoprotein remnants produced.

Busse-Buschke disease  cryptococcosis.

Caffey's disease  infantile cortical hyperostosis.

calcium hydroxyapatite deposition disease  apatite deposition d.

calcium pyrophosphate deposition disease  (CPDD) an acute or chronic inflammatory arthropathy caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the joints, chondrocalcinosis, and crystals in the synovial fluid. Acute attacks are sometimes called pseudogout.

Calvé-Perthes disease  osteochondrosis of capitular epiphysis of femur.

Camurati-Engelmann disease  diaphyseal dysplasia.

Canavan disease , Canavan-van Bogaert-Bertrand disease spongy degeneration of the central nervous system.

Carrión's disease  bartonellosis.

Castleman disease  a benign or premalignant condition resembling lymphoma but without recognizable malignant cells; there are isolated masses of lymphoid tissue and lymph node hyperplasia, usually in the abdominal or mediastinal area.

cat-scratch disease  a usually benign, self-limited disease of the regional lymph nodes, caused by Bartonella henselae and characterized by a papule or pustule at the site of a cat scratch, subacute painful regional lymphadenitis, and mild fever.

celiac disease  a malabsorption syndrome precipitated by ingestion of gluten-containing foods, with loss of villous structure of the proximal intestinal mucosa, bulky, frothy diarrhea, abdominal distention, flatulence, weight loss, and vitamin and electrolyte depletion.

Chagas disease  trypanosomiasis due to Trypanosoma cruzi; its course may be acute, subacute, or chronic.

Charcot-Marie-Tooth disease  muscular atrophy of variable inheritance, beginning in the muscles supplied by the peroneal nerves and progressing to those of the hands and arms.

cholesteryl ester storage disease  (CESD) a lysosomal storage disease due to deficiency of lysosomal cholesterol esterase, variably characterized by some combination of hepatomegaly, hyperbetalipoproteinemia, and premature atherosclerosis.

Christmas disease  hemophilia B.

chronic granulomatous disease  frequent, severe infections of the skin, oral and intestinal mucosa, reticuloendothelial system, bones, lungs, and genitourinary tract associated with a genetically determined defect in the intracellular bactericidal function of leukocytes.

chronic obstructive pulmonary disease  (COPD) any disorder marked by persistent obstruction of bronchial air flow.

Coats' disease  exudative retinopathy.

collagen disease  any of a group of diseases characterized by widespread pathologic changes in connective tissue; they include lupus erythematosus, dermatomyositis, scleroderma, polyarteritis nodosa, thrombotic purpura, rheumatic fever, and rheumatoid arthritis. Cf. collagen disorder.

communicable disease  a disease the causative agents of which may pass or be carried from one person to another directly or indirectly.

Concato's disease  progressive malignant polyserositis with large effusions into the pericardium, pleura, and peritoneum.

constitutional disease  one involving a system of organs or one with widespread symptoms.

Cori's disease  glycogen storage d., type III.

coronary artery disease  (CAD) atherosclerosis of the coronary arteries, which may cause angina pectoris, myocardial infarction, and sudden death; risk factors include hypercholesterolemia, hypertension, smoking, diabetes mellitus, and low levels of high-density lipoproteins.

coronary heart disease  (CHD) ischemic heart d.

Cowden disease  a hereditary disease marked by multiple ectodermal, mesodermal, and endodermal nevoid and neoplastic anomalies.

Creutzfeldt-Jakob disease  a rare prion disease existing in sporadic, familial, and infectious forms, with onset usually in middle life, and having a wide variety of clinical and pathological features. The most commonly seen are spongiform degeneration of neurons, neuronal loss, gliosis, and amyloid plaque formation, accompanied by rapidly progressive dementia, myoclonus, motor disturbances, and encephalographic changes, with death occurring usually within a year of onset.

Crigler-Najjar disease  see under syndrome.

Crohn's disease  regional enteritis; a chronic granulomatous inflammatory disease usually in the terminal ileum with scarring and thickening of the wall, often leading to intestinal obstruction and formation of fistulas and abscesses.

Crouzon's disease  craniofacial dysostosis.

Cruveilhier's disease  spinal muscular atrophy.

Cushing's disease  Cushing's syndrome in which the hyperadrenocorticism is secondary to excessive pituitary secretion of adrenocorticotropic hormone.

cystic disease of breast  mammary dysplasia with formation of blue dome cysts.

cytomegalic inclusion disease , cytomegalovirus disease an infection due to cytomegalovirus and marked by nuclear inclusion bodies in enlarged infected cells. In the congenital form, there is hepatosplenomegaly with cirrhosis, and microcephaly with mental or motor retardation. Acquired disease may cause a clinical state similar to infectious mononucleosis. When acquired by blood transfusion, postperfusion syndrome results.

deficiency disease  a condition caused by dietary or metabolic deficiency, including all diseases due to an insufficient supply of essential nutrients.

degenerative joint disease  osteoarthritis.

Dejerine's disease , Dejerine-Sottas disease progressive hypertrophic neuropathy.

demyelinating disease  any condition characterized by destruction of the myelin sheaths of nerves.

disappearing bone disease  gradual resorption of a bone or group of bones, sometimes associated with multiple hemangiomas, usually in children or young adults and following trauma.

diverticular disease  a general term including the prediverticular state, diverticulosis, and diverticulitis.

Duchenne's disease 

1. spinal muscular atrophy.

2. progressive bulbar paralysis.

3. tabes dorsalis.

4. Duchenne's muscular dystrophy.

Duchenne-Aran disease  spinal muscular atrophy.

Duhring's disease  dermatitis herpetiformis.

Dukes' disease  a febrile disease of childhood marked by an exanthematous eruption, probably due to a virus of the Coxsackie-ECHO group.

Durand-Nicolas-Favre disease  lymphogranuloma venereum.

Duroziez's disease  congenital mitral stenosis.

Ebola virus disease  fatal acute hemorrhagic fever resembling Marburg virus disease but caused by Ebola virus, seen in the Sudan and Zaire.

Ebstein's disease  see under anomaly.

end-stage renal disease  chronic irreversible renal failure.

Erb's disease  Duchenne's muscular dystrophy.

Erb-Goldflam disease  myasthenia gravis.

Eulenburg's disease  paramyotonia congenita.

extrapyramidal disease  any of a group of clinical disorders marked by abnormal involuntary movements, alterations in muscle tone, and postural disturbances; they include parkinsonism, chorea, athetosis, etc.

Fabry's disease  an X-linked lysosomal storage disease of glycosphingolipid catabolism resulting from deficiency of α-galactosidase A and leading to accumulation of ceramide trihexoside in the cardiovascular and renal systems.

Farber's disease  a lysosomal storage disease due to defective ceramidase and characterized by hoarseness, aphonia, dermatitis, bone and joint deformities, granulomatous reaction, and psychomotor retardation.

Fazio-Londe disease  a rare type of progressive bulbar palsy occurring in childhood.

Feer disease  acrodynia.

fibrocystic disease of breast  a form of mammary dysplasia with formation of cysts of various size containing a semitransparent, turbid fluid that imparts a brown to blue color to the unopened cysts; believed due to abnormal hyperplasia of the ductal epithelium and dilatation of the ducts of the mammary gland, resulting from exaggeration and distortion of normal menstrual cycle–related breast changes.

fibrocystic disease of the pancreas  cystic fibrosis.

fifth disease  erythema infectiosum.

flint disease  chalicosis.

floating beta disease  familial dysbetalipoproteinemia.

focal disease  a localized disease.

foot-and-mouth disease  an acute, contagious viral disease of wild and domestic cloven-footed animals and occasionally humans, marked by vesicular eruption on the lips, buccal cavity, pharynx, legs, and feet.

Forbes' disease  glycogen storage d., type III.

fourth disease  Dukes' d.

fourth venereal disease  granuloma inguinale.

Fox-Fordyce disease  a persistent and recalcitrant, itchy, papular eruption, chiefly of the axillae and pubes, due to inflammation of apocrine sweat glands.

Freiberg's disease  osteochondrosis of the head of the second metatarsal bone.

Friedländer's disease  endarteritis obliterans.

Friedreich's disease  paramyoclonus multiplex.

functional disease  see under disorder.

Garré's disease  sclerosing nonsuppurative osteomyelitis.

gastroesophageal reflux disease  (GERD) any condition resulting from gastroesophageal reflux, characterized by heartburn and regurgitation; see also reflux esophagitis.

Gaucher's disease  a hereditary disorder of glucocerebroside metabolism, marked by the presence of Gaucher's cells in the marrow, and by hepatosplenomegaly and erosion of the cortices of long bones and pelvis. The adult form is associated with moderate anemia and thrombocytopenia, and yellowish pigmentation of the skin; in the infantile form there is, in addition, marked central nervous system impairment; in the juvenile form there are rapidly progressive systemic manifestations but moderate central nervous system involvement.

genetic disease  a general term for any disorder caused by a genetic mechanism, comprising chromosome aberrations (or anomalies), mendelian (or monogenic or single-gene) disorders, and multifactorial disorders.

gestational trophoblastic disease  see under neoplasia.

Gilbert disease  a familial, benign elevation of bilirubin levels without evidence of liver damage or hematologic abnormalities.

Gilles de la Tourette's disease  see under syndrome.

Glanzmann disease  see thrombasthenia.

glycogen storage disease  any of a number of rare inborn errors of metabolism caused by defects in specific enzymes or transporters involved in the metabolism of glycogen.

type I glucose-6-phosphatase deficiency: a severe hepatorenal form due to deficiency of the hepatic enzyme glucose-6-phosphatase, resulting in liver and kidney involvement, with hepatomegaly, hypoglycemia, hyperuricemia, and gout

type IA glycogen storage d., type I.

type IB a form resembling type I but additionally predisposing to infection due to neutropenia and to chronic inflammatory bowel disease; due to a defect in the transport system for glucose 6-phosphate.

type II a disorder due to deficiency of the lysosomal enzyme α-1,4,-glucosidase, the severe infant form resulting in generalized glycogen accumulation, with cardiomegaly, cardiorespiratory failure, and death, and a milder adult form being a gradual skeletal myopathy that sometimes causes respiratory problems.

type III a form due to deficiency of debrancher enzyme (amylo-1,6-glucosidase) in muscle, liver, or both; defects in the liver enzyme are characterized by hepatomegaly and hypoglycemia while defects in the muscle enzyme are characterized by progressive muscle wasting and weakness.

type IV brancher enzyme deficiency; cirrhosis of the liver, hepatosplenomegaly, progressive hepatic failure, and death due to deficiency of the glycogen brancher enzyme (1,4-α-glucan branching enzyme).

type V muscle cramps and fatigue during exercise due to a defect in the skeletal muscle isozyme of glycogen phosphorylase (muscle phosphorylase).

type VI hepatomegaly, mild to moderate hypoglycemia and mild ketosis, due to deficiency of the liver isozyme of glycogen phosphorylase (hepatic phosphorylase).

type VII muscle weakness and cramping after exercise due to deficiency of the muscle isozyme of 6-phosphofructokinase.

type VIII phosphorylase .

graft-versus-host (GVH) disease  disease caused by the immune response of histoincompatible, immunocompetent donor cells against the tissue of immunocompromised host, as a complication of bone marrow transplantation, or as a result of maternal-fetal blood transfusion, or therapeutic transfusion to an immunocompromised recipient.

Graves' disease  an association of hyperthyroidism, goiter, and exophthalmos, with accelerated pulse rate, profuse sweating, nervous symptoms, psychic disturbances, emaciation, and elevated basal metabolism.

Greenfield's disease  former name for the late infantile form of metachromatic leukodystrophy.

Gull's disease  atrophy of the thyroid gland with myxedema.

Günther disease  congenital erythropoietic porphyria.

H disease  Hartnup d.

Hailey-Hailey disease  benign familial pemphigus.

Hallervorden-Spatz disease  an autosomal recessive disorder caused by decreased numbers of myelin sheaths of the globus pallidus and substantia nigra, with accumulation of iron pigment, progressive rigidity beginning in the legs, choreoathetoid movements, dysarthria, and mental deterioration.

Hand's disease  Hand-Schüller-Christian d.

hand-foot-and-mouth disease  a mild, highly infectious viral disease of children, with vesicular lesions in the mouth and on the hands and feet.

Hand-Schüller-Christian disease  a chronic, progressive form of multifocal Langerhans cell histiocytosis, sometimes with accumulation of cholesterol, characterized by the triad of calvarial bone defects, exophthalmos, and diabetes insipidus.

Hansen's disease  leprosy.

Hartnup disease  a hereditary disorder of intestinal and renal transport of neutral α-amino acids, marked by a pellagra-like skin rash, with transient cerebellar ataxia, constant renal aminoaciduria, and other biochemical abnormalities.

Hashimoto's disease  a progressive disease of the thyroid gland with degeneration of its epithelial elements and replacement by lymphoid and fibrous tissue.

heavy chain diseases  a group of malignant neoplasms of lymphoplasmacytic cells marked by the presence of immunoglobulin heavy chains or heavy chain fragments; they are classified according to heavy chain type, e.g., alpha chain disease.

Heine-Medin disease  the major form of poliomyelitis.

hemoglobin disease  any of various hereditary molecular diseases characterized by abnormal hemoglobins in the red blood cells; the homozygous form is manifested by hemolytic anemia.

hemolytic disease of the newborn  erythroblastosis fetalis.

hemorrhagic disease of the newborn  a self-limited hemorrhagic disorder of the first few days of life, due to deficiency of vitamin K–dependent coagulation factors II, VII, IX, and X.

Hers' disease  glycogen storage d., type VI.

Heubner-Herter disease  the infantile form of celiac disease.

hip-joint disease  tuberculosis of the hip joint.

Hippel's disease  von Hippel's d.

Hirschsprung's disease  congenital megacolon.

His disease , His-Werner disease trench fever.

Hodgkin's disease  a form of malignant lymphoma marked clinically by painless, progressive enlargement of lymph nodes, spleen, and general lymphoid tissue; other symptoms may include anorexia, lassitude, weight loss, fever, pruritus, night sweats, and anemia. Reed-Sternberg cells are characteristically present. Four types have been distinguished on the basis of histopathologic criteria.

hoof-and-mouth disease  foot-and-mouth d.

hookworm disease  infection with the hookworm Ancylostoma duodenale or Necator americanus, whose larvae enter the body through the skin or in contaminated food or water and migrate to the small intestine where, as adults, they attach to the mucosa and ingest blood; symptoms may include abdominal pain, diarrhea, colic or nausea, and anemia.

hyaline membrane disease  a type of respiratory distress syndrome of the newborn in which there is formation of a hyaline-like membrane lining the terminal respiratory passages; extensive atelectasis is attributed to lack of surfactant.

hydatid disease  an infection, usually of the liver, due to larval forms of tapeworms of the genus Echinococcus, marked by development of expanding cysts.

hypophosphatemic bone disease  an inherited disorder resembling a mild form of X-linked hypophosphatemia, similarly due to a defect in renal tubular function but usually showing osteomalacia without radiographic evidence of rickets.

immune complex disease  local or systemic disease caused by the formation of circulating immune complexes and their deposition in tissue, due to activation of complement and to recruitment and activation of leukocytes in type III hypersensitivity reactions.

infectious disease  one due to organisms ranging in size from viruses to parasitic worms; it may be contagious in origin, result from nosocomial organisms, or be due to endogenous microflora from the nose and throat, skin, or bowel.

inflammatory bowel disease  any idiopathic inflammatory disease of the bowel, such as Crohn's disease and ulcerative colitis.

intercurrent disease  one occurring during the course of another disease with which it has no connection.

iron storage disease  hemochromatosis.

ischemic bowel disease  ischemic colitis.

ischemic heart disease  (IHD) any of a group of acute or chronic cardiac disabilities resulting from insufficient supply of oxygenated blood to the heart.

Janský-Bielschowsky disease  the late infantile form of neuronal ceroid lipofuscinosis, occurring between two and four years of age, characterized by abnormal accumulation of lipofuscin; beginning as myoclonic seizures and progressing to neurologic and retinal deterioration and death by age 8 to 12.

jumping disease  any of several culture-specific disorders characterized by exaggerated responses to small stimuli, muscle tics including jumping, obedience even to dangerous suggestions, and sometimes coprolalia or echolalia.

juvenile Paget disease  hyperostosis corticalis deformans juvenilis.

Kashin-Bek (Kaschin-Beck) disease  a disabling degenerative disease of the peripheral joints and spine, endemic in northeastern Asia; believed to be caused by ingestion of cereal grains infected with the fungus Fusarium sporotrichiella.

Katayama disease  schistosomiasis japonica.

Kawasaki disease  a febrile illness usually affecting infants and young children, with conjunctival injection, changes to the oropharyngeal mucosa, changes to the peripheral extremities including edema, erythema, and desquamation, a primarily truncal polymorphous exanthem, and cervical lymphadenopathy. It is often associated with vasculitis of the large coronary vessels.

Kienböck's disease  slowly progressive osteochondrosis of the lunate bone; it may affect other wrist bones.

kinky hair disease  Menkes' syndrome.

Köhler's bone disease 

1. osteochondrosis of the tarsal navicular bone in children.

2. thickening of the shaft of the second metatarsal bone and changes about its articular head, with pain in the second metatarsophalangeal joint on walking or standing.

Krabbe's disease  a lysosomal storage disease beginning in infancy, due to deficiency of β-galactosidase. Pathologically, there is rapidly progressive cerebral demyelination and large globoid bodies (swollen with accumulated cerebroside) in the white substance.

Kufs' disease  the adult form of neuronal ceroid lipofuscinosis, with onset prior to age 40; characterized by progressive neurologic deterioration but not blindness, excessive storage of lipofuscin, and shortened life expectancy;

Kümmell's disease  compression fracture of vertebra, with symptoms a few weeks after injury, including spinal pain, intercostal neuralgia, lower limb motor disturbances, and kyphosis.

Kyasanur Forest disease  a fatal viral disease of monkeys in the Kyasanur Forest of India, communicable to humans, in whom it produces hemorrhagic symptoms.

Kyrle's disease  a chronic disorder of keratinization marked by keratotic plugs that develop in hair follicles and eccrine ducts, penetrating the epidermis and extending down into the corium, causing foreign-body reaction and pain.

Lafora's disease  see under epilepsy.

Leber's disease 

1. Leber's hereditary optic neuropathy.

2. Leber's congenital amaurosis.

legionnaires' disease  an often fatal bacterial infection caused by Legionella pneumophila, not spread by person-to-person contact, characterized by high fever, gastrointestinal pain, headache, and pneumonia; there may also be involvement of the kidneys, liver, and nervous system.

Leiner's disease  a disorder of infancy characterized by generalized seborrhea-like dermatitis and erythroderma, severe intractable diarrhea, recurrent infections, and failure to thrive.

Leriche disease  post-traumatic osteoporosis.

Letterer-Siwe disease  a Langerhans cell histiocytosis of early childhood, of autosomal recessive inheritance, characterized by cutaneous lesions resembling seborrheic dermatitis, hemorrhagic tendency, hepatosplenomegaly, lymphadenitis, and progressive anemia. If untreated it is rapidly fatal. Called also acute disseminated Langerhans cell histiocytosis.

Libman-Sacks disease  see under endocarditis.

Lindau's disease , Lindau-von Hippel disease von Hippel-Lindau d.

Little's disease  congenital spastic stiffness of the limbs, a form of cerebral palsy due to lack of development of the pyramidal tracts.

Lobstein's disease  see osteogenesis imperfecta.

Lou Gehrig disease  amyotrophic lateral sclerosis.

Lowe disease  oculocerebrorenal syndrome.

Lutz-Splendore-Almeida disease  paracoccidioidomycosis.

Lyme disease  a recurrent multisystemic disorder caused by the spirochete Borrelia burgdorferi, the vectors being the ticks Ixodes scapularis and I. pacificus; usually initially characterized by lesions of erythema chronicum migrans, followed by various manifestations including arthritis of the large joints, myalgia, and neurologic and cardiac abnormalities.

lysosomal storage disease  an inborn error of metabolism with (1) a defect in a specific lysosomal enzyme; (2) intracellular accumulation of an unmetabolized substrate; (3) clinical progression affecting multiple tissues or organs; (4) considerable phenotypic variation within a disease.

MAC disease  complex d.

McArdle disease  glycogen storage d., type V.

mad cow disease  bovine spongiform encephalopathy.

Madelung's disease 

1. see under deformity.

2. see under neck.

maple bark disease  hypersensitivity pneumonitis in logging and sawmill workers due to inhalation of spores of a mold, Cryptostroma corticale, growing under the maple bark.

maple syrup urine disease  (MSUD) a hereditary enzyme defect in metabolism of branched chain amino acids, marked clinically by mental and physical retardation, severe ketoacidosis, feeding difficulties, and a characteristic maple syrup odor in the urine and on the body.

Marburg virus disease  a severe, often fatal, viral hemorrhagic fever first reported in Marburg, Germany, among laboratory workers exposed to African green monkeys.

Marchiafava-Micheli disease  paroxysmal nocturnal hemoglobinuria.

Marie-Bamberger disease  hypertrophic pulmonary osteoarthropathy.

Marie-Strümpell disease  ankylosing spondylitis.

Marie-Tooth disease  Charcot-Marie-Tooth d.

Mediterranean disease  thalassemia major.

medullary cystic disease  familial juvenile nephronophthisis.

Meniere's disease  deafness, tinnitus, and dizziness, in association with nonsuppurative disease of the labyrinth.

mental disease  see under disorder.

Merzbacher-Pelizaeus disease  Pelizaeus-Merzbacher d.

metabolic disease  one caused by a disruption of a normal metabolic pathway because of a genetically determined enzyme defect.

Meyer's disease  adenoid vegetations of the pharynx.

Mikulicz's disease  benign, self-limited lymphocytic infiltration and enlargement of the lacrimal and salivary glands of uncertain etiology.

Milroy disease  hereditary permanent lymphedema of the legs due to lymphatic obstruction.

Minamata disease  a severe neurologic disorder due to alkyl mercury poisoning, with permanent neurologic and mental disabilities or death; once prevalent among those eating contaminated seafood from Minamata Bay, Japan.

minimal change disease  subtle alterations in kidney function demonstrable by clinical albuminuria and the presence of lipid droplets in cells of the proximal tubules, seen primarily in young children.

mixed connective tissue disease  a combination of scleroderma, myositis, systemic lupus erythematosus, and rheumatoid arthritis, and marked serologically by the presence of antibody against extractable nuclear antigen.

Möbius disease  ophthalmoplegic migraine.

molecular disease  any disease in which the pathogenesis can be traced to a single molecule, usually a protein, which is either abnormal in structure or present in reduced amounts.

Mondor's disease  phlebitis affecting the large subcutaneous veins normally crossing the lateral chest wall and breast from the epigastric or hypochondriac region to the axilla.

Monge's disease  chronic mountain sickness.

Morquio's disease , Morquio-Ullrich disease see under syndrome.

motor neuron disease , motor system disease any disease of a motor neuron, including spinal muscular atrophy, progressive bulbar paralysis, amyotrophic lateral sclerosis, and lateral sclerosis.

Mycobacterium avium complex disease  MAC disease; systemic disease caused by infection with organisms of the Mycobacterium avium-intracellulare complex in patients with human immunodeficiency virus infection.

Newcastle disease  a viral disease of birds, including domestic fowl, transmissible to humans, characterized by respiratory, gastrointestinal or pulmonary, and encephalitic symptoms.

new variant Creutzfeldt-Jakob disease  (nvCJD) a variant of Creutzfeldt-Jakob disease having a younger age of onset than is seen in Creutzfeldt-Jakob disease, and caused by the same agent that causes bovine spongiform encephalopathy.

Nicolas-Favre disease  lymphogranuloma venereum.

Niemann's disease , Niemann-Pick disease a lysosomal storage disease due to sphingomyelin accumulation in the reticuloendothelial system; there are five types distinguished by age of onset, amount of central nervous system involvement, and degree of enzyme deficiency.

nil disease  minimal change d.

Norrie's disease  an X-linked disorder consisting of bilateral blindness from retinal malformation, mental retardation, and deafness.

notifiable disease  one required to be reported to federal, state, or local health officials when diagnosed, because of infectiousness, severity, or frequency of occurrence.

oasthouse urine disease  methionine malabsorption syndrome.

obstructive small airways disease  chronic bronchitis with irreversible narrowing of the bronchioles and small bronchi with hypoxia and often hypercapnia.

occupational disease  disease due to various factors involved in one's employment.

Oguchi's disease  a form of hereditary night blindness and fundus discoloration following light adaptation.

organic disease  one associated with demonstrable change in a bodily organ or tissue.

Osgood-Schlatter disease  osteochondrosis of the tuberosity of the tibia.

Osler's disease 

1. polycythemia vera.

2. hereditary hemorrhagic telangiectasia.

Owren's disease  parahemophilia.

Paget's disease 

1. (of bone) osteitis deformans.

2. (of breast) an intraductal inflammatory carcinoma of the breast, involving the areola and nipple.

3. an extramammary counterpart of Paget's disease (2), usually involving the vulva, and sometimes other sites, as the perianal and axillary regions.

Parkinson's disease  a slowly progressive form of parkinsonism, usually seen late in life, marked by masklike facies, tremor of resting muscles, slowing of voluntary movements, festinating gait, peculiar posture, muscular weakness, and sometimes excessive sweating and feelings of heat.

Parrot's disease  see under pseudoparalysis.

parrot disease  psittacosis.

Parry's disease  Graves' d.

Pelizaeus-Merzbacher disease  a progressive familial form of leukoencephalopathy, marked by nystagmus, ataxia, tremor, parkinsonian facies, dysarthria, and mental deterioration.

Pellegrini's disease , Pellegrini-Stieda disease calcification of the medial collateral ligament of the knee due to trauma.

pelvic inflammatory disease  (PID) any pelvic infection involving the upper female genital tract beyond the cervix.

periodontal disease  any disease or disorder of the periodontium.

Perthes' disease  osteochondrosis of capitular femoral epiphysis.

Peyronie's disease  induration of the corpora cavernosa of the penis, producing a painful fibrous chordee and penile curvature.

Pfeiffer's disease  infectious mononucleosis.

Pick's disease 

1. progressive atrophy of the cerebral convolutions in a limited area (lobe) of the brain, with clinical manifestations and course similar to Alzheimer's disease.

2. Niemann-Pick d.

polycystic kidney disease , polycystic disease of kidneys either of two unrelated heritable disorders marked by cysts in both kidneys: the autosomal dominant or adult form is more common, appears in adult life, and is marked by loss of renal function that can be either rapid or slow; the autosomal recessive or infantile form is more rare, may be congenital or may appear later in childhood, and almost always progresses to renal failure.

polycystic renal disease  polycystic kidney d..

Pompe's disease  glycogen storage d., type II.

Pott's disease  spinal tuberculosis.

primary electrical disease  serious ventricular tachycardia, and sometimes ventricular fibrillation, in the absence of recognizable structural heart disease.

prion disease  any of a group of fatal, transmissible neurodegenerative diseases, which may be sporadic, familial, or acquired, caused by abnormalities of prion protein metabolism resulting from mutations in the prion protein gene or from infection with pathogenic forms of the protein.

pulseless disease  Takayasu's arteritis.

Raynaud's disease  a primary or idiopathic vascular disorder, most often affecting women, marked by bilateral attacks of Raynaud's phenomenon.

Recklinghausen's disease 

1. neurofibromatosis.

2. (of bone) osteitis fibrosa cystica generalisata.

Refsum's disease  an inherited disorder of lipid metabolism, characterized by accumulation of phytanic acid, chronic polyneuritis, retinitis pigmentosa, cerebellar ataxia, and persistent elevation of protein in cerebrospinal fluid.

remnant removal disease  familial dysbetalipoproteinemia.

reversible obstructive airway disease  a condition characterized by bronchospasm reversible by intervention, as in asthma.

rheumatic heart disease  the most important manifestation and sequel to rheumatic fever, consisting chiefly of valvular deformities.

rheumatoid disease  a systemic condition best known by its articular involvement (rheumatoid arthritis) but emphasizing nonarticular changes, e.g., pulmonary interstitial fibrosis, pleural effusion, and lung nodules.

Ritter's disease  dermatitis exfoliativa neonatorum.

Roger's disease  a ventricular septal defect; the term is usually restricted to small, asymptomatic defects.

runt disease  a graft-versus-host disease produced by immunologically competent cells in a foreign host that is unable to reject them, resulting in gross retardation of host development and in death.

Salla disease  an inherited disorder of sialic acid metabolism characterized by accumulation of sialic acid in lysosomes and excretion in the urine, mental retardation, delayed motor development, and ataxia.

Sandhoff's disease  a type of GM2 gangliosidosis resembling Tay-Sachs disease, seen in non-Jews, marked by a progressively more rapid course, and due to a defect in hexosaminidase, both isozymes A and B.

Schamberg's disease  a slowly progressive purpuric and pigmentary disease of the skin affecting chiefly the shins, ankles, and dorsa of the feet.

Schilder's disease  subacute or chronic leukoencephalopathy in children and adolescents, similar to adrenoleukodystrophy; massive destruction of the white substance of the cerebral hemispheres leads to blindness, deafness, bilateral spasticity, and mental deterioration.

Schönlein's disease  see under purpura.

secondary disease 

1. one subsequent to or as a consequence of another disease.

2. one due to introduction of incompatible, immunologically competent cells into a host rendered incapable of rejecting them by heavy exposure to ionizing radiation.

self-limited disease  one that runs a limited and definite course.

serum disease  see under sickness.

severe combined immunodeficiency disease  (SCID) see under immunodeficiency .

sexually transmitted disease  venereal disease; any of a diverse group of infections transmitted by sexual contact; in some this is the only important mode of transmission, and in others transmission by nonsexual means is possible.

sickle cell disease  any disease associated with the presence of hemoglobin S.

Simmonds' disease  see panhypopituitarism.

sixth disease  exanthema subitum.

small airways disease  chronic obstructive bronchitis with irreversible narrowing of the bronchioles and small bronchi. See also obstructive small airways d.

Smith-Strang disease  methionine malabsorption syndrome.

Spielmeyer-Vogt disease  Vogt-Spielmeyer d.

Steinert's disease  myotonic dystrophy.

Still's disease  juvenile rheumatoid arthritis.

storage disease  a metabolic disorder in which a specific substance (a lipid, a protein, etc.) accumulates in certain cells in unusually large amounts.

storage pool disease  a blood coagulation disorder due to failure of the platelets to release adenosine diphosphate (ADP) in response to aggregating agents; characterized by mild bleeding episodes, prolonged bleeding time, and reduced aggregation response to collagen or thrombin.

Strümpell's disease 

1. hereditary lateral sclerosis with the spasticity mainly limited to the legs.

2. cerebral poliomyelitis.

Strümpell-Leichtenstern disease  hemorrhagic encephalitis.

Strümpell-Marie disease  ankylosing spondylitis.

Sutton's disease 

1. halo nevus.

2. periadenitis mucosa necrotica recurrens.

3. granuloma fissuratum.

Swift's disease , Swift-Feer disease acrodynia.

Takayasu's disease  see under arteritis .

Tangier disease  a familial disorder characterized by a deficiency of high-density lipoproteins in the blood serum, with storage of cholesteryl esters in tissues.

Tarui's disease  glycogen storage d., type VII.

Tay-Sachs disease  (TSD) the most common GM2 gangliosidosis, seen almost exclusively in northeastern European Jews, characterized by infantile onset, doll-like facies, cherry-red macular spot, early blindness, hyperacusis, macrocephaly, seizures, hypotonia, and death in early childhood.

Thomsen's disease  myotonia congenita.

thyrotoxic heart disease  heart disease associated with hyperthyroidism, marked by atrial fibrillation, cardiac enlargement, and congestive heart failure.

transmissible neurodegenerative disease  prion d..

trophoblastic disease  gestational trophoblastic neoplasia.

tsutsugamushi disease  scrub typhus.

tunnel disease  decompression sickness.

uremic bone disease  renal osteodystrophy.

venereal disease  sexually transmitted d.

venoocclusive disease of the liver  symptomatic occlusion of the small hepatic venules caused by ingestion of Senecio tea or related substances, by certain chemotherapy agents, or by radiation.

vinyl chloride disease  acro-osteolysis resulting from exposure to vinyl chloride, characterized by Raynaud's phenomenon and skin and bony changes on the limbs.

Vogt-Spielmeyer disease  the juvenile form of neuronal ceroid lipofuscinosis with onset between ages 5 and 10 years; characterized by rapid cerebroretinal degeneration, excessive neuronal storage of lipofuscin, and death within 10 to15 years.

Volkmann's disease  congenital deformity of the foot due to tibiotarsal dislocation.

von Hippel's disease  hemangiomatosis confined principally to the retina; when associated with hemangioblastoma of the cerebellum, it is known as von Hippel-Lindau d.

von Hippel-Lindau disease  a hereditary condition marked by hemangiomas of the retina and hemangioblastomas of the cerebellum, sometimes with similar lesions of the spinal cord and cysts of the viscera; there may be neurologic symptoms such as seizures and mental retardation.

von Willebrand's disease  an autosomal dominant bleeding disorder characterized by prolonged bleeding time, deficiency of von Willebrand's factor, and often impairment of adhesion of platelets on glass beads, associated with epistaxis and increased bleeding after trauma or surgery, menorrhagia, and postpartum bleeding.

Waldenström's disease  osteochondrosis of the capitular femoral epiphysis.

Weber-Christian disease  nodular nonsuppurative panniculitis.

Werlhof's disease  idiopathic thrombocytopenic purpura.

Wernicke's disease  see under encephalopathy.

Westphal-Strümpell disease  hepatolenticular degeneration.

Whipple's disease  a malabsorption syndrome marked by diarrhea, steatorrhea, skin pigmentation, arthralgia and arthritis, lymphadenopathy, central nervous system lesions, and infiltration of the intestinal mucosa with macrophages containing PAS-positive material.

Whitmore's disease  melioidosis.

Wilson's disease  an inherited, progressive disorder of copper metabolism, with accumulation of copper in liver, brain, kidney, cornea, and other tissues; it is characterized by cirrhosis in the liver, degenerative changes in the brain, and a pigmented ring at the outer margin of the cornea.

Wolman's disease  a lysosomal storage disease due to deficiency of the lysosomal sterol esterase, occurring in infants, and associated with hepatosplenomegaly, adrenal steatorrhea, calcification, abdominal distention, anemia, and inanition.

woolsorter's disease  inhalational anthrax.

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sickle cell disease

n.

See sickle cell anemia.

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sickle cell disease,

any of the diseases associated with the presence of hemoglobin S and sickle cells, including hemoglobin SC disease, hemoglobins D disease, sickle cell anemia, and sickle cell thalassemia.

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disease(s) (dizēz´),

n a definite deviation from the normal state characterized by a series of symptoms. Disease may be caused by developmental disturbances, genetic factors, metabolic factors, living agents, or physical, chemical, or radiant energy, or the cause may be unknown.

disease, Adams-Stokes (Adams-Stokes syndrome),

n.pr a disease characterized by a slow and perhaps irregular pulse, vertigo, syncope, occasional pseudoepileptic convulsions, and Cheyne-Stokes respirations.

disease, adaptation (adaptation syndrome),

n the metabolic disorders occurring as a result of adaptation or resistance to severe physical or psychologic stress. See also syndrome, general adaptation.

disease, Addison's,

n.pr a chronic adrenocortical insufficiency caused by bilateral tuberculosis, aplasia, atrophy, or degeneration of the adrenal glands. Symptoms include severe weakness, weight loss, low blood pressure, digestive disturbances, hypoglycemia, lowered resistance to infection, and abnormal pigmentation (bronze color of the skin, with associated melanotic pigmentation of the oral mucosa, especially of the gingival tissues).

disease, adrenocortical,

n the disorders of adrenocortical function, giving rise to Addison's disease, Cushing's syndrome, adrenogenital syndrome, and primary aldosteronism.

disease, Albers-Schönberg,

n.pr See osteopetrosis.

disease, autoallergic,

n See disease, autoimmune.

disease, autoimmune (autoallergic disease, autoimmunization syndrome, chronic hypersensitivity),

n a disease that is believed to be caused in part by reactions of hypersensitivity of the host tissue (antigens). Includes various hemolytic anemias, idiopathic thrombocytopenias, rheumatoid arthritis, systemic lupus erythematosus, glomerulonephritis, scleroderma, Hashimoto's thyroiditis, and Sjögren's syndrome.

disease, Barlow's,

n.pr See scurvy, infantile.

disease, Basedow's,

n.pr See goiter, exophthalmic.

disease, Behçet's,

n.pr See syndrome, Behçet's.

disease, Besnier-Boeck-Schaumann,

n.pr See sarcoidosis.

disease, bleeder's,

n See hemophilia.

disease, blood,

n a disease affecting the hematologic system (e.g., anemia, leukemia, agranulocytosis purpura, infectious mononucleosis). Such a disease often results in lesions of the oral structures, particularly the mucosal surfaces.

disease, Bowen's,

n.pr See carcinoma in situ.

disease, Brill-Symmers,

n.pr See lymphoblastoma, giant follicular.

disease, brittle bone,

n See osteogenesis imperfecta.

disease, Caffey's,

n.pr See hyperostosis, infantile cortical.

disease, Cannon's,

n.pr See nevus, white sponge.

disease, cardiac,

n a disease affecting the heart.

disease, cat-scratch,

n a granulomatous disease caused by
B. henselae that occurs at the site of a scratch or bite of a house cat. Local lesions occur at the site of injury with a regional adenitis that is out of proportion to the primary lesion occurring within 1 to 3 weeks. Systemic symptoms of infection may occur. Diagnosis is confirmed by serologic tests.

Cat-scratch disease.

disease, celiac,

n See celiac sprue.

disease, Cheadle's,

n.pr See scurvy, infantile.

disease, Christmas,

n.pr See hemophilia B.

disease, chronic hypersensitivity,

n See disease, autoimmune.

disease, chronic obstructive pulmonary (COPD),

n a disease marked by decreased expiratory flow rates resulting in increased total lung capacity. Patients with this condition are prone to acute respiratory failure from infections or general anesthesia.

disease, collagen (group disease, visceral angiitis)

(kol´jin),
n a group of diseases affecting the collagenous connective tissue of several organs and systems. These diseases have similar biochemical structural alterations and include rheumatic fever, scleroderma, rheumatoid arthritis, systemic lupus erythematosus, periarteritis, and serum sickness.

diseases, communicable,

n a disease that may be transmitted directly or indirectly to a well person or animal from an infected person or animal. A disease with the capacity for maintenance by natural modes of spread (e.g., by contact, by airborne routes, through drinking water or food, by arthropod vectors).

disease, congenital,

n a disease present at birth, or, more specifically, one that is acquired in utero.

disease, Coxsackie A,

n.pr See herpangina.

disease, Crouzon,

n.pr See syndrome, Crouzon.

disease, Cushing's,

n.pr hypercortisolism that results from an adrenal or pituitary neoplasm. The term
Cushing's syndrome refers to hypercortisolism that is not related to an endogenous process.

disease, cytomegalic inclusion, generalized,

n See disease, salivary gland.

disease, Darier's (keratosis follicularis),

n.pr an apparently genetic dermatologic disease that also involves mucous membranes. The oral lesions are whitish papules of the gingiva, tongue, or palate. It is characterized histologically by the presence of corps ronds.

disease, deficiency,

n a disturbance produced by lack of nutritional or metabolic factors. Used mainly in reference to avitaminosis.

disease, degenerative joint,

n See osteoarthritis.

disease, dermatologic,

n a disease affecting the skin; often accompanied by pathologic manifestations of various mucosal surfaces (e.g., the oral mucosa, genital mucosa, conjunctiva).

disease, end-stage,

n the last phase of an illness, at which point the patient's life is gravely endangered.

disease, Engman's,

n.pr See dermatitis infectiosa eczematoides.

disease, exanthematous

n a group of diseases caused by a number of viruses but having as a prominent feature a skin rash (e.g., smallpox, chickenpox, cowpox, measles, rubella).

disease, familial,

n a disease occurring in several members of the same family. Often used to mean members of the same generation and occasionally used synonymously with hereditary disease.

disease, Feer's,

n.pr See erythredema polyneuropathy and acrodynia.

disease, fibrocystic (mucoviscidosis)

(fī´brōsis´tik mū´kōvis´idō´sis),
n a hereditary defect of most of the exocrine glands in the body, including the salivary glands. The secretion of the affected mucous glands is abnormally viscous.

disease, fifth,

n a viral infection caused by the human parvovirus B19; spread via the upper respiratory tract, this virus impacts on children more strongly than adults. Also called
erythema infectiosum.

disease, Fordyce's,

n.pr See Fordyce granules.

disease, functional,

n a disease that has no observable or demonstrable cause.

disease, Gaucher's

(gôshāz´),
n.pr a constitutional defect in the metabolism of the cerebroside kerasin. This glycoprotein accumulates in the reticuloendothelial system and leads to splenomegaly, hepatomegaly, lymph node enlargement, and bone defects.

disease, graft-versus-host (GVHD),

n a potentially deadly condition resulting from allogenically transplanted hematopoietic cells that reject host cells in the transplant recipient. In early stages, this condition may result in lichenoid and erosive lesions on the oral mucosa.

disease, Graves',

n.pr See goiter, exophthalmic.

disease, hand-foot-and-mouth (aphthous fever, epidemic stomatitis, epizootic stomatitis)

(af´ths),
n primarily a disease of animals caused by a filterable virus that may be transmitted to humans and that occasionally produces symptoms. The human form is characterized by fever, nausea, vomiting, malaise, and ulcerative stomatitis. Skin lesions consisting of vesicles may appear, usually on the palms of the hands and soles of the feet. Spontaneous regression usually occurs within 2 weeks.

Hand, foot, and mouth disease.

disease, Hand-Schūller-Christian (chronic disseminated histiocytosis X),

n.pr a type of cholesterol lipoidosis characterized clinically by defects in membranous bones, exophthalmos, and diabetes insipidus.

disease, Hansen's,

n.pr See leprosy.

disease, heart,

n an abnormal condition of the heart (organic, mechanical, or functional) that causes difficulty.

disease, heart, arteriosclerotic,

n a variety of functional changes of the myocardium that result from arteriosclerosis.

disease, heart, congenital,

n a defective formation of the heart or of the major vessels of the heart.

disease, heart, ischemic

(iskē´mik),
n a heart condition in which an inadequate supply of oxygenated blood reaches the heart, resulting in damage to the heart muscle; it is usually caused by atherosclerosis, a buildup of fatty plaque deposits in the main coronary arteries that leads to narrowing or hardening of the arteries. Symptoms include chest pain or discomfort (angina pectoris), ventricular fibrillation, heart attack (myocardial infarction), or sudden death. Also known as
coronary artery disease and
coronary heart disease.

disease, heart, rheumatic,

n a scarring of the endocardium resulting from involvement in acute rheumatic fever. The process most often involves the mitral valve.

disease, heart, thyrotoxic

n cardiac failure occurring as the result of hyperthyroidism or its superimposition on existing organic heart disease. Thyrotoxicosis is an important cause of auricular fibrillation.

disease, hemoglobin C,

n a disease resulting from an abnormal hemoglobin (hemoglobin C); occurs primarily in African Americans and causes a mild normochromic anemia, target cells, and vague, intermittent arthralgia.

disease, hemolytic, of newborn,

n a hemolysis caused by isoimmune reactions associated with Rh incompatibility or with blood transfusions in which there is an incompatibility of the ABO blood system. Several forms of the disease occur: erythroblastosis fetalis, congenital hemolytic disease, icterus gravis neonatorum, and hydrops fetalis.

disease, hemophilioid

n a hemophilic states (conditions) that clinically resemble hemophilia (e.g., parahemophila, hemophilia B [Christmas disease]).

disease, hemorrhagic, of newborn

(hem´raj´ik),
n a hemorrhagic tendency in newborn infants occurring usually on the third or fourth day of life; believed to be caused by defects of prothrombin and factor VII, resulting from a deficiency of vitamin K.

disease, hereditary,

n a disease transmitted from parent to offspring through genes. Three main types of mendelian heredity are recognized: dominant, recessive, and sex-linked.

disease, hidebound,

n See scleroderma.

disease, Hodgkin,

n.pr See lymphoma, Hodgkin.

disease, hypersensitivity,

n See disease, autoimmune.

disease, iatrogenic

(īat´rjen´ik),
n a disease arising as a result of the actions or words of a health care professional.

disease, idiopathic

n a disease in which the etiology is not recognized or determined.

disease, infectious,

n the pathologic alterations induced in the tissues by the action of microorganisms and/or their toxins. Some infectious diseases involving the oral tissues are herpes zoster, herpetic gingivostomatitis, moniliasis, syphilis, and tuberculosis.

disease, inflammatory neoplastic,

n See granuloma; tumor, inflammatory.

disease, kissing,

n See mononucleosis, infectious.

disease, Langerhans cell (Langerhans cell histiocytosis),

n a group of three diseases identified by an abundance of Langerhans cells–eosinophils combined with histiocytic cells. See also disease, Letterer-Siwe; disease, Hand-Schūller-Christian; and granuloma, eosinophili.

disease, Letterer-Siwe

n.pr (acute disseminated histiocytosis X, nonlipid histiocytosis, nonlipid reticuloendotheliosis), a fatal febrile disease of unknown cause occurring in infants and children; characterized by focal granulomatous lesions of the lymph nodes, spleen, and bone marrow. Results in enlargement of the lymph nodes, spleen, and liver, defects of the flat and long bones, anemia, and sometimes purpura.

disease, lipoid storage (lipoidosis, reticuloendothelial granuloma)

(lip´oid ritik´ylōen´dōthē´lēl gran´ylō´m lipoidō´sis),
n group of diseases in which lipid substances accumulate in the fixed cells of the reticuloendothelial system. Included are Gaucher's disease, Niemann-Pick disease, and the Hand-Schūller-Christian disease complex. Other storage diseases include lipochondrodystrophy (gargoylism) and cerebral sphingolipidosis.

disease, Lobstein's,

n.pr See osteogenesis imperfecta.

disease, macrovascular,

n a disease of the large blood vessels, including the aorta, and coronary arteries. Fatty plaque buildup and thrombosis formation in these vessels may lead to a myocardial infarction, cerebral infarction, and circulation problems in the limbs. It is often a complication of long-term diabetes.

disease, Marie's,

n.pr See acromegaly.

disease, Mediterranean,

n.pr See thalassemia major.

disease, metabolic bone,

n.pl the diseases of the bone which may be attributed to cellular changes or to nutritional deficiencies/excesses brought on by dietary imbalances. These include hyperparathyroidism, osteoporosis, osteomalacia, rickets, and the many diseases associated with an abnormal abundance of Langerhans cells.

disease, Mikulicz'

(mik´ūlich´z),
n.pr a benign hyperplasia of the lymph nodes of the parotid or other salivary glands and/or the lacrimal glands.

disease, Moeller's,

n.pr See scurvy, infantile.

disease, molecule,

n a disease associated with genetically determined abnormalities of protein synthesis at the molecular level.

disease, muscle,

n the pathologic muscle tissue changes that can lead to disease. Such changes reveal few structural alterations, and the highly differentiated contents of muscle fibers tend to react as a whole. The pathologic features that distinguish one muscle disease from another are the age and character of changes within a muscle, distribution of those changes within one or several muscles, presence of inflammatory cells and parasites, and coexistence of pathologic changes in other organs. Muscles undergo a number of degenerative changes. There are alterations in the striation in certain pathologic states caused by cloudy swelling, granular degeneration, waxy or hyaline degeneration, and other cellular modifications such as multiplication of the sarcolemmic nuclei and phagocytosis of muscle fibers.

disease, neuromuscular,

n a condition in which various areas of the central nervous system are affected; results in dysfunction or degeneration of the musculature and disabilities of the organ.

disease, Niemann-Pick

n.pr a congenital, familial disorder occurring mainly in Jewish female infants that terminates fatally before the third year and is characterized by the accumulation of the phospholipid sphingomyelin in the cells of the reticuloendothelial system.

disease, oral, hereditary,

n the heritable defects of oral and paraoral structures (excluding the dentition) without generalized defects; includes ankyloglossia, hereditary gingivofibromatosis, and possibly cleft lip and cleft palate. Many oral and paraoral defects are associated with generalized defects (e.g., Peutz-Jeghers, Franceschetti, Ehlers-Danlos, Pierre Robin, and Sturge-Weber syndromes; hemorrhagic telangiectasia; Crouzon's disease; sickle cell disease; acatalasemia; white spongy nevus; xeroderma pigmentosum; gargoylism; neurofibromatosis; familial amyloidosis; and achondroplasia).

disease, oral manifestations of systemic,

n the lesions in association with systemic disease, often influenced by the local environmental factors within the oral cavity.

disease, organic,

n a disease in which actual structural changes have occurred in the organs or tissues.

disease, Osler's,

n.pr See erythremia.

disease, Owren's,

n.pr See parahemophilia.

disease, Paget's, of bone (osteitis deformans),

n.pr a bone disease characterized by thickening and bowing of the long bones and enlargement of the skull and maxillae. It is represented radiographically by a cotton-wool appearance of the bone and microscopically by a mosaic bone pattern with so-called reversal lines. Hypercementosis and loosening of the teeth may be significant manifestations. Increased serum alkaline phosphatase may be an early finding.

Paget's disease of the bone.

disease, Parkinson's,

n.pr a progressive neurologic disorder for which there is no known cure that is thought to be the result of neuron degeneration in the section of the brain controlling spontaneous movement and balance. The disease causes postural changes, tremors, muscle rigidity, and weakness. Oral manifestations include difficulty in swallowing and excess salivation.

disease, periodic,

n See disorder(s), periodic.

disease, periodontal

n a disturbance of the periodontium. Diseases affecting the periodontium include aggressive and necrotizing types, as well as gingivitis. Etiologic factors may be local or systemic or may involve an interplay between the two. Periodontal diseases may be involved in increasing the risk and course of systemic diseases.

disease, periodontal, etiologic factors of,

n.pl the local and systemic factors, singly or in combination, that initiate periodontal lesions.

disease, periodontal, local factors of,

n.pl the environmental conditions within the oral cavity that initiate, enable, or alter the course of diseases of the periodontium (e.g., calculus, diastemata between teeth, food impaction, prematurities in the centric path of closure, and tongue habits).

disease, peripheral vascular,

n a disease of arteries, veins, and/or lymphatic vessels.

disease, pink,

n See acrodynia.

disease, Pott's,

n.pr a spinal curvature (kyphosis) resulting from tuberculosis.

disease progression,

n the course of the disease within a patient/host from onset to resolution.

disease, psychosomatic

(sī´kōsōmat´ik),
n a disease that appears to have been precipitated or prolonged by emotional stress; manifested largely through the autonomic nervous system. Various conditions may be included (e.g., certain forms of asthma, dermatosis, migraine headache, and hypertension). See also disorder, psychophysiologic, autonomic, and visceral.

disease, Quincke's,

n.pr See edema, angioneurotic.

disease, Rendu-Osler-Weber (ron´doo),

n.pr See telangiectasia, hereditary hemorrhagic.

disease, rheumatic,

n See rheumatism.

disease, rickettsial

(riket´sēl),
n a disease caused by microorganisms of the order Rickettsiales (e.g., Rocky Mountain spotted fever, rickettsialpox, typhus, and Q fever).

disease, Riga-Fede

(rē´g-fā´d), an ulceration of the lingual frenum of infants caused by abrasion by natal or neonatal teeth.

disease, Sainton's,

n.pr See dysplasia, cleidocranial.

disease, salivary gland (generalized cytomegalic inclusion),

n a generalized infection in infants caused by intrauterine or postnatal infection with a cytomegalovirus of the group of herpesviruses. Manifestations include jaundice, purpura, hemolytic anemia, vomiting, diarrhea, chronic eczema, and failure to gain weight.

disease, Schūller's

n.pr See osteoporosis.

disease, Selter's,

n.pr See acrodynia.

disease, sex-linked,

n a hereditary disorder transmitted by the gene that also determines sex (e.g., hemophilia).

disease, sickle cell,

n a hematologic disorder caused by the presence of an abnormal hemoglobin (hemoglobin S) that permits the formation or results in the formation of sickle-shaped red blood cells. Two forms of the disease occur: sickle cell trait and sickle cell anemia. See also anemia, sickle cell; trait, sickle cell.

disease, Simmonds' (pituitary cachexia, hypophyseal cachexia, hypopituitary cachexia),

n.pr a panhypopituitarism resulting from destruction of the pituitary gland, usually from hemorrhage or infarction.

disease, Sturge-Weber-Dimitri (encephalotrigeminal angiomatosis),

n.pr See angiomatosis, Sturge-Weber.

disease susceptibility,

n the degree to which a patient or host is vulnerable to a disease.

disease, Sutton's,

n.pr See periadenitis mucosa necrotica recurrens.

disease, Swift's,

n.pr See acrodynia.

disease, systemic,

n a disease involving the whole body.

disease, Takahara's

n.pr a form of rare progressive oral gangrene occurring in childhood and seen only in Japan. Apparently related to a congenital lack of the enzyme catalase (acatalasemia). Characterized by a mild to severe form of a peculiar type of oral gangrene that may develop at the roots of the teeth or the tonsils. Loss of teeth occurs, with necrosis of the alveolar bone. Patients become symptom free after puberty.

disease, transmissible,

n a disease capable of being transmitted from one individual to another; a disease capable of being maintained in successive passages through a susceptible host, usually under experimental conditions such as by injection. See also disease, communicable.

disease transmission,

n the method by which a disease is passed from one patient or host to another. The three most common methods of transmission are direct contact, aerosols, and vectors, such as insects.

disease, Vaquez'

n.pr See erythremia.

disease vectors,

n.pl the intermediary hosts that carry the disease from one species to another, such as mosquitoes, ticks, and rabid animals.

disease, von Recklinghausen's,

n.pr See hyperparathyroidism; osteitis; generalized fibrosa cystica; and neurofibromatosis.

disease, von Recklinghausen's, of bone

(fōn rek´linghouzenz),
n.pr See hyperparathyroidism; osteitis fibrosa cystica.

disease, von Recklinghausen's, of skin,

n.pr See neurofibromatosis.

disease, von Willebrand's

(fōn vil´ebränts),
n.pr an inherited blood coagulation disorder attributed to a deficiency or malfunction of factor VIII. It may cause prolonged or excessive gingival bleeding.

disease, Weil's (epidemic jaundice)

n.pr an acute febrile disease caused by
Leptospira icterohaemorrhagiae or
L. canicola. Manifestations include fever, petechial hemorrhage, myalgia, renal insufficiency, hepatic failure, and jaundice.

disease, Werlhof's

(verl´hofs),
n.pr See purpura, thrombocytopenic.

diseases, demyelinating

n the diseases that have in common a loss of myelin sheath, with preservation of the axis cylinders (e.g., multiple sclerosis, Schilder's disease).

diseases, dental, hereditary,

n.pl the heritable defects of the dentition without generalized disease, which include amelogenesis imperfecta, dentinogenesis imperfecta, dentinal dysplasia, localized and generalized hypoplasia of enamel, peg-shaped lateral incisors, familial dentigerous cysts, missing teeth, giantism, and fused primary mandibular incisors. Dental defects occurring with generalized disease include dentinogenesis imperfecta with osteogenesis imperfecta, missing teeth with ectodermal dysplasia, enamel hypoplasia with epidermolysis bullosa dystrophica, retarded eruption with cleidocranial dysostosis, missing lateral incisors with ptosis of the eyelids, missing premolars with premature whitening of the hair, and enamel hypoplasia in vitamin D resistant rickets.

diseases, group,

n See disease, collagen.

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sickle cell disease

Any syndrome associated with sickle cells–eg, sickle cell anemia–hemoglobin genotype S/S, sickle cell-HbC disease, sickle cell-β-thalassemia Management Allogeneic BMTP may be curative in young Pts with symptomatic SCD. See Sickle cell anemia.

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Patient discussion about sickle cell disease.

Q. Please precribe for me the possible medicine (treatment) for sickle cells. Secondly, my boy lost hearing at 4 1- I need to know how sickle cells can be treated. 2- My boy just surprisingly lost his abillity to hear anything at the age of 4.

A. wow...you are going through some hard times...it's the hardest thing in the world seeing your children in pain. loosing his hearing could be caused by clots that were formed and destroyed the ear nerve. but it's unlikely it happened in both ears...so i would check it out. and about treatment- there are a variety of treatments, so i found a web site with them all. and even some that are still in research: http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_Treatments.html