Endocrine disease in adrenoleukodystrophy

X-linked adrenoleukodysrophy is the most frequent genetic disorder affectin g central and peripheral nervous system myelin. One of the biochemical abno rmalities is the accumulation of very long chain fatty acids (VLCFA) in tis sues and body fluids subsequent to defective catabolism in the peroxysomes. The principal characteristic of the disease is an association between a ne urological disorder and an endocrine disorder: primary adrenal insufficienc y and testicular failure. Clinical manifestations are variable. There are t wo main forms, one affecting boys between the age of 5 and 10 years with se vere rapidly fatal cerebral involvement, and the other affecting young adul ts between the age of 20 and 30 years with degeneration of the anterior and posterior long spinal cord tracts, similar to the disorders observed in mu ltiple sclerosis. About 20% of the heterozygous women may develop a syndrom e which resembles adrenomyeloneuropathy, rarely adrenal insufficiency. Adrenal insufficiency is present in 85% of the childhood cerebral forms and in about 70% of the adult forms. It may occur before, after or at the same time as the neurological disease but is not correlated,vith the severity o f the neurological disorder. Careful screening is required to avoid missing subclinical forms. Adrenoleukodystrophy should be envisaged in young boys with primary adrenal insufficiency, accounting for about 30% of the cases o f primary adrenal insufficiency in children under 3 years of age and about 13% of those in adults. Experience with dietary therapy (low-VLCFA diet and supplementation with un saturated fatty acids such as glyceryl trioleate (GTO) and glyceryl trieruc ate (GTE), commonly tailed Lorenzo's oil) has not demonstrated any clinical improvement in the cerebral forms. Bone marrow transplantation is recommen ded for children who show early evidence of cerebral involvement. Gene ther apy is a promising perspective. Lovastatin and 4-phenlbutyrate have recentl y been shown to normalize plasma VLCFA levels. Their therapeutic efficacy m ust be assessed in a randomized trial.