Adrenoleukodystrophy

Adrenoleukodystrophy (ALD) is a degenerative disorder of the sheath covering nerve fibers, known as myelin. A type of leukodystrophy, the victims of ALD are typically male, as the disease is usually inherited in a sex-linked manner on the X chromosome. Leukodystrophies are disorders that affect the growth and/or development 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. Leukodystrophies are different from demyelinating disorders such as multiple sclerosis, in which myelin is formed normally, but is lost by immunologic dysfunction or 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 (normally less than 20). This was originally described by Moser et al in 1981.

Related Topics:
X-linked - X chromosome - Fatty acids - Carbon

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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 (Mosser et al 1993). A dysfunctional gene leads to the accumulation of long-chain fatty acids.

Related Topics:
Peroxisome - Organelle - Oxidation

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The precise mechanisms through which high VLCFA concentrations cause the disease are still (2005) unknown, but accumulation is severe in the organs affected.

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