Adrenoleukodystrophy
| Adrenoleukodystrophy | |
| ICD-10 | E71.3 |
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| ICD-9 | 330.0, 277.86 |
| OMIM | 300100 202370 |
| DiseasesDB | 292 |
| MeSH | D000326 |
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Adrenoleukodystrophy Microchapters |
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Diagnosis |
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Treatment |
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Adrenoleukodystrophy On the Web |
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American Roentgen Ray Society Images of Adrenoleukodystrophy |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords:: Adrenoleucodystrophy, adrenomyeloneuropathy, bronze schilder disease, siemerling-creutzfeldt disease, addison-schilder syndrome
Overview
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.
Pathophysiology
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.[1] 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.[2] 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.
Symptoms
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.
Diagnosis
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.
Histopathology: Adrenoleukodystrophy of Brain
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Treatment
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;[3] 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.
References
- ↑ Moser HW, Moser AB, Frayer KK, Chen W, Schulman JD, O'Neill BP, Kishimoto Y. Adrenoleukodystrophy: increased plasma content of saturated very long chain fatty acids. Neurology 1981;31:1241-9. PMID 7202134.
- ↑ Mosser J, Douar AM, Sarde CO, Kioschis P, Feil R, Moser H, Poustka AM, Mandel JL, Aubourg P. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 1993;361:726-30. PMID 8441467.
- ↑ Moser HW, Raymond GV, Lu S-E, Muenz LR, Moser AB, Xu J, Jones RO, Loes DJ, Melhem ER, Dubey P, Bezman L, Brereton NH, Odone A. Follow-up of 89 asymptomatic patients with adrenoleukodystrophy treated with Lorenzo's Oil. Arch Neurol 2005;62;1073-80. PMID 16009761.
External links
- Adrenoleukodystrophy at National Center for Biotechnology Information
- US Patent 5,331,009 — Patent to Croda International Plc on treating ALD with special oil composition inspired by Augusto Odone
Template:Metabolic pathology Template:Peroxisomal disorders
de:Adrenoleukodystrophie hr:Adrenoleukodistrofija it:Adrenoleucodistrofia he:ALD fi:ALD sv:Adrenoleukodystrofi