Adrenoleukodystrophy (ALD) is a degenerative disorder of myelin, a complex fatty neural tissue that insulates many nerves of the central and peripheral nervous systems. Without myelin, nerves are unable to conduct an impulse, leading to increasing disability as myelin destruction increases and intensifies. The victims of ALD are always male, and the disease begins its expression around the ages 5 to 10. The disease is due to an X-linked inheritance of peroxisomes that cannot properly process long chain fatty acids in the brain.ALD is a type of leukodystrophy, disorders affecting the growth and/or development of myelin. Leukodystrophies are different from demyelinating disorders such as multiple sclerosis where myelin is formed normally but is lost by immunologic dysfunction or for other reasons.
The clinical presentation is largely dependent on the age of onset of the disease. The most severe type is the childhood cerebral form, which normally occurs in males between the ages of 5 and 10 and is characterized by failure to develop, seizures, ataxia, adrenal insufficiency, as well as degeneration of visual and auditory function. This form can also occur in adolescents and very rarely in adults. In another form of ALD, which primarily strikes young men, the spinal cord dysfunction is more prominent and therefore is called adrenomyeloneuropathy, or "AMN." The patients usually present with weakness and numbness of the limbs and urination or defecation problems. Most victims of this form are also males, although some female carriers exhibit symptoms similar to AMN. Adult and neonatal (which tend to affect both males and females and be inherited in an autosomal recessive manner) forms of the disease also exist but they are extremely rare. Some patients may present with sole findings of adrenal insufficiency (Addison's disease). ALD also causes uncontrollable rage in some cases.
The diagnosis is established by clinical findings and the detection of serum long chain fatty acid levels. MRI examination reveals white matter abnormalities, and neuroimaging findings of this disease are quite reminiscent of the findings of multiple sclerosis. Genetic testing for the analysis of the defective gene is available in some centers.
The most common form of ALD is X-linked (the defective gene is on the X chromosome, location Xq28), and is characterized by excessive accumulation of very long chain fatty acids (VLCFA) — fatty acids chains with 24–30 carbon atoms (particularly hexacosanoate, C26) in length. This was originally described by Moser et al in 1981. So, when the ALD gene was discovered in 1993, it was a surprise that the corresponding protein was in fact a member of a family of transporter proteins, not an enzyme. It is still a mystery as to how the transporter affects the function of the fatty acid enzyme and, for that matter, how high levels of very long chain fatty acids cause the loss of myelin on nerve fibers. The gene (ABCD1 or "ATP-binding cassette, subfamily D, member 1") codes for a protein that transfers fatty acids into peroxisomes, the cellular organelles where the fatty acids undergo β-oxidation. A dysfunctional gene leads to the accumulation of very long chain fatty acids (VLCFA). The precise mechanisms through which high VLCFA concentrations cause the disease are still unknown as of 2005, but accumulation is severe in the organs affected. The prevalence of X-linked adrenoleukodystrophy is approximately 1 in 20,000 individuals. This condition occurs with a similar frequency in all populations.
While there is currently no cure for the disease, some dietary treatments, for example, Lorenzo's oil in combination with a diet low in VLCFA, have been used with limited success, especially before disease symptoms appear. A recent study by Moser et al (2005) shows positive long-term results with this approach; see also the Myelin Project. Bone marrow transplantation has been proven to help ALD who are either presymptomatic or exhibiting mild symptoms early in the course of the disease. Lovastatin is an anticholesterol drug that seems to help, but researchers aren't sure how or why. Treatment, however, is to AID the symptoms and is NOT a cure.
Adrenoleukodystrophy: A rare genetic (inherited) disorder characterized by the breakdown or loss of the myelin sheath surrounding nerve cells in the brain and progressive dysfunction of the adrenal gland. Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath of the nerve fibers in the brain. The myelin sheath is a fatty covering which acts as an electrical insulator.
The classic childhood form, which is the most severe and affects only boys, may occur between ages 4 and 10. It affects only boys because the gene is on the X chromosome. Features of this form may include visual loss, learning disabilities, seizures, dysarthria (poorly articulated speech), dysphagia (difficulty swallowing), deafness, disturbances of gait and coordination, fatigue, intermittent vomiting, melanoderma (increased skin pigmentation), and progressive dementia. The most common symptoms are usually behavioural changes such as abnormal withdrawal or aggression, poor memory, and poor school performance.
Another form of ALD is occasionally seen in women who are carriers of the disorder. Symptoms are mild and may include spastic paraparesis of the lower limbs, ataxia, hypertonia (excessive muscle tone), mild peripheral neuropathy, and urinary problems. The milder adult-onset form typically begins between ages 21 and 35. Symptoms may include leg stiffness, progressive spastic paraparesis (stiffness, weakness and/or paralysis) of the lower extremities, and ataxia. Although adult-onset ALD progresses more slowly than the classic childhood form, it can also result in deterioration of brain function. Neonatal (newborn) ALD affects both male and female babies. Symptoms may include mental retardation, facial abnormalities, seizures, retinal degeneration, hypotonia (low muscle tone), hepatomegaly (enlarged liver), and adrenal dysfunction. This form is usually quickly progressive. The treatment for all forms of ALD is symptomatic and supportive. Physical therapy, psychological support, and special education may be useful for some individuals. The prognosis for patients with ALD is generally poor due to progressive neurological deterioration. Death usually occurs within 1 to 10 years after the onset of symptoms
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