Clinical and therapeutic aspects of adrenoleukodystrophy and adrenomyeloneuropathy

Adrenoleukodystrophy (ALD) and its adult variant adrenomyeloneuropathy (AMN) are X-linked diseases in which a deficiency of lignoceroyl-CoA ligase, a peroxisomal enzyme needed for the degradation of very long chain fatty acids (VLCFA), has been reported. The responsible gene recently has been cloned; it codes for a peroxisomal membrane protein, ALDP, which is a member of the ABC (ATP binding cassette) transporter superfamily. Elevations in VLCFA, particularly C24 and C26, have proven useful in the diagnosis of the childhood, adolescent and adult cerebral forms and AMN. ALD and AMN commonly coexist in the same families; the same VLCFA elevations and gene mutations have been recognized in both ALD and AMN. This phenotypic heterogeneity suggests the influence of an autosomal modifier gene. Dietary manipulation using glyceryl trioleate-trieurucate oil (Lorenzo's oil) has been highly successful in lowering VLCFA, but not in affecting the rate of neurologic deterioration in symptomatic ALD boys or AMN adults. Dietary pretreatment of neurologically asymptomatic ALD patients may have some benefit and is advisable at the present time. Currently, we recommend bone marrow transplantation for those patients who show evidence of early cerebral involvement and for whom a well-matched donor is available. A drug therapy trial utilizing beta interferon and thalidomide is underway.