Adrenoleukodystrophy (ALD) refers to several different inherited conditions that affect the nervous system and adrenal glands. Other names for it are adrenomyeloneuropathy, childhood cerebral ALD, and Schilder-Addison Complex. The gene that causes ALD was identified in 1993. It occurs in about 1 in 20,000 people and mainly affects men. Women can carry ALD without having any symptoms. The symptoms, treatments, and prognosis of ALD vary depending on which type is present. ALD is not curable, but the progression can be slowed in some cases.
The genetic bases for all different phenotypic variants of X-ALD are mutations in the gene encoding the peroxisomal ATP-binding cassette (ABC) transporter, ABCD1 (formerly adrenoleukodystrophy protein, ALDP). ABCD1 transports CoA-activated very long-chain fatty acids from the cytosol into the peroxisome for degradation. The phenotypic variability is remarkable ranging from cerebral inflammatory demyelination of childhood onset, leading to death within a few years, to adults remaining pre-symptomatic through more than five decades. There is no general genotype-phenotype correlation in X-ALD.
The minimum incidence of affected males in the United States is estimated to be 1 per 21,000 males, and the combined incidence of affected males and heterozygous women in the total USA population 1:16,800. Somewhat higher figures have been obtained in France, with the most recent estimate of affected males set at 1:15,000 males. Kondrashov estimated that the mutation rate of ABCD1 is 2.64 times 10-8. X-ALD has been observed in all ethnic groups, without evidence of differential rates (Kondrashov 2003). Only 1.7% of affected males have been found to have new mutations. An extended family screening led to the identification of 594 additional affected males, 250 of them asymptomatic, at a time when therapy has the greatest chance of being beneficial, and 1,270 heterozygotes.