adrenoleukodystrophy(redirected from Siemerling-Creutzfeldt Disease)
Adrenoleukodystrophy is a rare genetic disease characterized by a loss of myelin surrounding nerve cells in the brain and progressive adrenal gland dysfunction.
Adrenoleukodystrophy (ALD) is a member of a group of diseases, leukodystrophies, that cause damage to the myelin sheath of nerve cells. Approximately one in 100,000 people is affected by ALD. There are three basic forms of ALD: childhood, adult-onset, and neonatal. The childhood form of the disease is the classical form and is the most severe. Childhood ALD is progressive and usually leads to total disability or death. It affects only boys because the genetic defect is sex-linked (carried on the X chromosome). Onset usually occurs between ages four and ten and can include many different symptoms, not all of which appear together. The most common symptoms are behavioral problems and poor memory. Other symptoms frequently seen are loss of vision, seizures, poorly articulated speech, difficulty swallowing, deafness, problems with gait and coordination, fatigue, increased skin pigmentation, and progressive dementia.
The adult-onset form of the disease, also called adrenomyeloneuropathy, is milder, progresses slowly, is usually associated with a normal life span, and usually appears between ages 21-35. Symptoms may include progressive stiffness, weakness, or paralysis of the lower limbs and loss of coordination. Brain function deterioration may also been seen. Women who are carriers of the disease occasionally experience the same symptoms, as well as others, including ataxia, hypertonia (excessive muscle tone), mild peripheral neuropathy, and urinary problems. The neonatal form affects both male and female infants and may produce mental retardation, facial abnormalities, seizures, retinal degeneration, poor muscle tone, enlarged liver, and adrenal dysfunction. Neonatal ALD usually progresses rapidly.
Causes and symptoms
The genetic defect in ALD causes a decrease in the ability to degrade very long chain fatty acids. These build up in the adrenal glands, brain, plasma, and fibroblasts. The build-up of very long chain fatty acids interferes with the ability of the adrenal gland to convert cholesterol into steroids and causes demyelination of nerves in the white matter of the brain. Demyelinated nerve cells are unable to function properly.
Diagnosis is made based on observed symptoms, a biochemical test, and a family history. The biochemical test detects elevated levels of very long chain fatty acids in samples from amniocentesis, chorionic villi, plasma, red blood cells, or fibroblasts. A family history may indicate the likelihood of ALD because the disease is carried on the X-chromosome by the female lineage of families.
Treatment for all forms of ALD consists of treating the symptoms and supporting the patient with physical therapy, psychological counseling, and special education in some cases. There is no cure for this disease, and there are no drugs that can reverse demyelination of nerve and brain cells. Dietary measures consist of reducing the intake of foods high in fat, which are a source of very long chain fatty acids. A mixture called Lorenzo's Oil has been shown to reduce the level of long chain fatty acids if used long term; however, the rate of myelin loss is unaffected. Experimental bone marrow transplantation has not been very effective.
Prognosis for childhood and neonatal ALD patients is poor because of the progressive myelin degeneration. Death usually occurs between one and ten years after onset of symptoms.
Since ALD is a genetic disease, prevention is largely limited to genetic counseling and fetal monitoring through amniocentesis or chorionic villus sampling.
Berkow, Robert. Merck Manual of Medical Information. Whitehouse Station, NJ: Merck Research Laboratories, 1997.
Amniocentesis — The collection of amniotic fluid through a needle inserted through the abdomen. Used to collect fetal cells for genetic analysis.
Ataxia — Loss of coordination of muscular movement.
Hypertonia — Having excessive muscular tone.
Myelin — A layer that encloses nerve cells and some axons and is made largely of lipids and lipoproteins.
Neuropathy — A disease or abnormality of the peripheral nerves.
an X-linked recessive disease of childhood, closely related to Schilder's disease, marked by diffuse abnormality of the cerebral white matter and adrenal atrophy with abnormal adrenal functioning; characteristics include mental deterioration progressing to dementia, with aphasia, apraxia, dysarthria, and loss of vision in about a third of patients.
a·dre·no·leu·ko·dys·tro·phy (ALD),(ă-drē'nō-lū-kō-dis'trŏ-fē), [MIM*300100]
An X-linked recessive disorder affecting male children, resulting from a defect in long-chain fatty acid metabolism and characterized by chronic adrenocortical insufficiency, skin hyperpigmentation, progressive dementia, spastic paralysis, and other intellectual and neurologic disturbances; results from myelin degeneration in the white matter of the brain. The causative gene maps to Xq and encodes adrenoleukodystrophy protein (ALDP), an ATP-binding transporter located in the peroxisomal membrane. A mild form of ALD affecting older male children, as well as adolescent or adult males is called adrenomyeloneuropathy
adrenoleukodystrophy/adre·no·leu·ko·dys·tro·phy/ (-loo″ko-dis´tro-fe) an X-linked disorder related to Schilder's disease, characterized by diffuse abnormality of the cerebral white matter with mental retardation and adrenal atrophy.
An X-linked form of leukodystrophy occurring chiefly in boys, characterized by accumulation of very long-chain fatty acids in the brain and adrenal cortex and resulting in adrenocortical insufficiency and progressive neurological deterioration.
a rare hereditary neonatal-childhood metabolic disorder that is transmitted as a recessive sex-linked trait and affects mainly males. It is characterized by adrenal atrophy and widespread cerebral demyelination, producing progressive mental deterioration, aphasia, apraxia, eventual blindness, and tetraplegia. In the neonate form the prognosis is poor, with death occurring usually in 1 to 5 years. The childhood form may be chronic and treatable for a few years with a special diet. ALD was formerly classified under Schilder's disease.
AdrenoleukodystrophyA usually X-linked leukodystrophy in which impaired oxidation of saturated very long-chain fatty acids (VLCFAs) is associated with adrenal insufficiency—Addison's disease—neurologic impairment, and, in late-onset cases, adrenomyeloneuropathy, which primarily affects young men, causing spinal cord dysfunction, weakness and paraesthesias of the extremities.
Clinical findings Onset at age 5 and 10 with reversal of neurologic milestones, seizures, ataxia, Addison's disease, degeneration of visual and auditory function.
Molecular pathology Defect in ABCD1 on chromosome Xq28, which encodes a peroxisome membrane protein (ALDP or ABCD1) necessary for VLCFA beta-oxidation. VLCFA accumulation leads to damage to the CNS, peripheral nervous system and adrenal gland.
Prognosis Dismal. The treatment is generally symptomatic. Pilot data from gene therapy has been promising, but is still inconclusive as of mid-2011.
Popular culture Lorenzo Odone (1978–2008) was a famous ALD patient whose parents drove the creation of a concoction of fatty acids (Lorenzo's Oil, which begat the film of the same name) that is still being studied as a possible therapy for ALD.
adrenoleukodystrophyMelanodermic leukodystrophy An X-linked peroxisomal disease in which impaired oxidation of saturated long-chain fatty acids is associated with adrenal insufficiency–Addison's disease and neurologic impairment, and in late-onset cases, adrenomyeloneuropathy. See Leukodystrophy.
Rare disease of the central nervous system characterized by progressive blindness, deafness, tonic spasms, mental retardation, and atrophy of the suprarenal gland; inherited as an X-linked recessive trait primarily affecting males.
adrenoleukodystrophyAn X-linked recessive peroxisome disorder affecting the adrenal glands and the white matter of the central nervous system. The disease features the accumulation of very long-chain fatty acids causing progressive dysfunction of these tissues by demyelinization. The disease usually manifests itself between the ages of 4 and 8 years and often leads to total disability within two years. Adult forms occur but are rare.
n rare childhood disease that affects boys; an inherited metabolic disorder in which patients often die within one to five years of diagnosis. Sym-ptoms include cerebral nerve damage, mental decline, apraxia, aphasia, blindness, and quadriplegia.