Gaucher disease

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Related to Gaucher disease: Niemann Pick disease

Gaucher Disease



Gaucher disease is a rare genetic disorder that results in accumulation of fatty molecules called cerebrosides. It can have serious effects on numerous body organs including the liver, spleen, bones and central nervous system. Treatments based on molecular biology are becoming available, but are very expensive.


Gaucher disease was first described by the French physician Philippe Gaucher in 1882. It is the most common of a class of diseases called lysosomal storage diseases, each of which is characterized by the accumulation of a specific chemical substance (a different substance depending on the exact disease). Gaucher disease is characterized by a wide array of different symptoms and the severity of the disease ranges from undetectable to lethal.
Three forms of the disease are recognized: Types I, II and III. Type I is by far the most common and shows the mildest symptoms. It is non-neuronopathic, meaning that the nervous system is not attacked. The onset of Type I can occur at any age in childhood or adult life with the average age of onset at about 21 years. Some affected individuals are have no symptoms throughout adult life. Type II, the infantile form, accounts for less than 1% of patients with Gaucher disease. It is neuronopathic (attacks the nervous system); nervous system effects are severe, and victims often die within the first year of life. Type III most often has its onset during childhood and has some of the features of both the adult and infantile forms. This affects less than 5% of persons with Gaucher disease.
Gaucher disease is caused by the absence, or near absence, of activity of an enzyme called glucocerebrosidase (GC). The normal action of GC is to break down a common molecule called glucocerebroside. If not broken down, glucocerebroside accumulates in certain cells to levels that can cause damage, especially in the spleen, liver, and bone. The common link among these organs is that they house a cell type called a macrophage. A macrophage is a large cell that surrounds and consumes a foreign substance (such as bacteria) in the body. The cellular structures in which glucocerebroside accumulates are called lysosomes.
The three forms of Gaucher disease also differ in their population genetics. Type I is most common in persons of eastern European (Ashkenazi) Jewish descent. Among this population, the disease occurs at a rate of one in 450 live births and about one in 10 to 15 persons are carriers, making it the most common genetic disease affecting Jewish people. The other two types are equally frequent in all ethnic groups. Type II occurs at a rate of one in 100,000 live births, while Type III is estimated to occur in one in 50,000 live births.

Causes and symptoms

Lack of the GC enzyme is caused by a mutation in the glucocerebrosidase gene. The gene is located on chromosome 1. As of 2000, there have been over 100 mutations described in this gene that causes Gaucher disease. Gaucher disease is inherited in an autosomal recessive pattern. This means that two defective gene copies must be inherited, one from each parent, for the disease to manifest itself. Persons with only one gene mutation are carriers for the disorder. A person who is a carrier for Gaucher disease does not have any symptoms and does not know he or she is a carrier unless he or she has had specific testing. When both parents are carriers for Gaucher disease, there is a one in four chance (25%) in each pregnancy for a child to have Gaucher disease. There is a two in three chance that a healthy sibling of an affected child is a carrier.
The results of Gaucher disease are widespread in the body and include excessive growth of the liver and spleen (hepatosplenomegaly), weakening of bones, and, in acute cases, severe nervous system damage. Many patients experience "bone crises," which are episodes of extreme pain in their bones.
There is a wide array of other problems that occur with Gaucher disease, such as anemia (fewer than normal red blood cells). Just how these other symptoms are caused is not known. Nor is it known why some patients have very mild disease and others have much more significant problems. Even identical twins with the disease can have differing symptoms.


Diagnosis of Gaucher disease, based initially on the symptoms described above, can be confirmed by microscopic, enzymatic, and molecular tests. Biopsy (surgical removal of tissue from a problem area) of tissue is helpful for microscopic diagnosis. When biopsy tissue is examined under the microscope, cells will appear swollen and will show characteristic features of the cytoplasm (part of the cell body along with the nucleus) and nucleus. Enzyme tests will show deficiency (<30% of normal levels) of the enzyme GC. Molecular analysis of DNA samples looking at four of the more common mutations will show defects in the gene for GC in 95% of Ashkenazi Jewish individuals and in 75% of non-Jewish people. Diagnosis can be performed prenatally (before birth) if the parents' mutations are known using amniocentesis or chorionic villus sampling.
Diagnosis as to which of the three types of Gaucher disease an individual has is based on the symptoms, rather than on test results.


Until the 1990s, only supportive therapy could be offered. Analgesics are used to control pain. Orthopedic treatment is used for bone fractures. In some cases, surgical removal of the spleen may be necessary. Several treatments for anemia have been used, including vitamin and iron supplements, blood transfusions, and bone marrow transplants.
The newest form of treatment for Gaucher disease is enzyme replacement therapy, in which GC can be administered intravenously. The enzyme can be prepared either by purification from placentas (alglucerase) or by recombinant DNA manufacturing techniques (imiglucerase). Either way, the cost of treatment ranges from $100,000 to $400,000 per year, which can prevent many from obtaining treatment.
Enzyme replacement is effective at reducing most Gaucher symptoms. The notable exception is neurologic damage in Type II disease, which remains unimproved by this treatment. This treatment is not recommended for individuals who are asymptomatic. As of 2000, the efficacy for the treatment of Type III Gaucher disease is not known. Many questions remain about enzyme replacement therapy in regard to dosage, and method and frequency of administration. The treatment program should be individualized for each patient.


A patient's expected lifespan varies greatly with the type of Gaucher disease. Infants with Type II disease have a life span of one to four years. Patients with Types I and III of the disease have highly variable outcomes with some patients dying in childhood and others living full lives. Little is known about the reasons for this variability.


Genetic counseling is advised for individuals with Gaucher disease and for their relatives to accurately assess risk and discuss testing options. For couples who previously had a child with Gaucher or in situations where both parents are carriers for known Gaucher mutations, prenatal diagnosis is available to determine whether a pregnancy is affected. Families in which a person has been diagnosed with Gaucher disease can have DNA testing, which enables other relatives to determine their carrier status. Prospective parents can then use that information to conduct family planning or to prepare for a child who may have special circumstances.
Families in which both parents are known to be a carrier of a mutation for Gaucher disease could consider preimplantation genetic diagnosis. This relatively new procedure can select an embryo without both Gaucher disease mutations prior to implantation of the embryo into the uterus. This technique is only available at selected genetics centers.
As of the early 2000s, population screening for Gaucher disease is not standard of care.

Key terms

Cerebrosides — Fatty carbohydrates that occur in the brain and nervous system.
Enzymatic replacement therapy — A treatment method used to replace missing enzymes. It is possible to synthesize enzymes and then inject them intravenously into patients.
Glucocerebroside — A cerebroside that contains glucose in the molecule.



Beutler, E. "Gaucher Disease." Archives of Internal Medicine 159 (1999): 881-2.


Alliance of Genetic Support Groups. 4301 Connecticut Ave. NW, Suite 404, Washington, DC 20008. (202) 966-5557. Fax: (202) 966-8553.
Children's Gaucher Research Fund. PO Box 2123, Granite Bay, CA 95746-2123. (916) 797-3700. Fax: (916) 797-3707.
National Gaucher Foundation. 11140 Rockville Pike, Suite 350, Rockville, MD 20852-3106. (800) 925-8885.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481.


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Gale Encyclopedia of Medicine. Copyright 2008 The Gale Group, Inc. All rights reserved.

Gauch·er dis·ease

a lysosomal storage disorder due to a deficiency of glucocerebrosidase resulting in accumulation of glucocerebroside; high incidence among Ashkenazi Jews; occurs most severely in infants, characterized by hepatosplenomegaly, hematologic abnormalities, bone lesions, neurologic manifestations with ataxia, spastic paraplegia, seizures, dementia, and presence of characteristic histiocytes (Gaucher cells) in the viscera; autosomal recessive inheritance, caused by mutation in the glucocerebrosidase A gene (GBA) on chromosome 1q. There are three main forms: type I, noncerebral juvenile [MIM*230800]; type II, cerebral juvenile [MIM*230900]; and type III, adult cerebral [MIM*231000]; the juvenile forms are most severe.
Farlex Partner Medical Dictionary © Farlex 2012

Gaucher disease

(gō-shā′) or

Gaucher's disease

A lysosomal storage disease characterized by enlargement of the liver and spleen, anemia, bone deterioration, and in certain types of the disease, neurological involvement.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.

Gauch·er dis·ease

(gō-shā' di-zēz')
A lysosomal storage disease resulting from glycocerebroside accumulation due to a genetic deficiency of glucocerebrosidase; may occur in adults but occurs most severely in infants; marked by hepatosplenomegaly, regression of neurologic maturation, and characteristic histiocytes (Gaucher cells) in the viscera.
Medical Dictionary for the Health Professions and Nursing © Farlex 2012


Philippe Charles Ernest, French physician, 1854-1918.
Gaucher cells - large, finely and uniformly vacuolated cells derived from the reticuloendothelial system and found especially in the spleen, lymph nodes, liver, and bone marrow of patients with Gaucher disease.
Gaucher disease - a lysosomal storage disease. Synonym(s): cerebroside lipidosis; familial splenic anemia
Gaucher type of histiocyte
pseudo-Gaucher cell - a plasma cell, microscopically resembling a Gaucher cell, found in the bone marrow in some cases of multiple myeloma.
Medical Eponyms © Farlex 2012

Gauch·er dis·ease

(gō-shā' di-zēz')
Lysosomal storage disorder due to deficiency of glucocerebrosidase resulting in accumulation of glucocerebroside.
Medical Dictionary for the Dental Professions © Farlex 2012
References in periodicals archive ?
Gaucher disease is an autosomal recessive lysosomal glycosphingolipid storage disorder resulting from a deficiency of the lysosomal enzyme acid P-glucosidase (glucocerebrosidase).
In Gaucher disease, ferritin levels are generally elevated without other biochemical evidence of iron overload, consistent with anemia of chronic disease, whereas typical iron deficiency anemia is characterized by low serum iron, low transferrin saturation and low ferritin levels (9).
Before start of therapy, G1cCer was higher in patients with Gaucher disease than in controls [mean concentration of G1cCer in plasma from controls was 6.3 (1.9) /[micro]mol/L (n = 40)].
Gaucher disease can have a profound impact on the musculoskeletal system.
Disorders associated with CSH include multiple myeloma/monoclonal gammopathies of undetermined significance, lymphoplasmacytic lymphoma (with or without Waldenstrom macroglobulinemia), and more rarely mucosa-associated lymphoid tissue lymphoma and amyloidosis.[7] It has been suggested that the reported associations between Gaucher disease and multiple myeloma represent cases of misdiagnosed CSH.[4] The pathogenesis of CSH begins with paraprotein, abnormal in amount and structure and produced by neoplastic cells, followed by phagocytosis by tissue macrophages.
Although most common among Jews of Eastern European (Ashkenazi) descent, Gaucher disease occurs in individuals of all ethnic groups.
Orphazyme is testing arimoclomol in four indications including amyotrophic lateral sclerosis (ALS), Niemann-Pick disease Type C (NPC), Gaucher disease and sporadic Inclusion Body Myositis (sIBM).
PR001 is a potentially disease-modifying, single-dose, AAV9-based gene therapy being developed for the treatment of PD-GBA and neuronopathic Gaucher disease. Following the FDA's acceptance of Prevail's Investigational New Drug application in June, the Company is on track to begin dosing patients in a Phase 1/2 clinical trial in the second half of 2019.
Lysosomal storage disorders and Parkinson's disease: Gaucher disease and beyond.