Adrenoleukodystrophy: From Bedside to Molecular Biology

Abstract

Although X-linked adrenoleukodystrophy was first described in 1923, the key advances in understanding the disorder followed discoveries beginning in 1973 that it was characterized by the tissue accumulation of very long chain fatty acids, particularly hexacosanoic acid (C26:0). Very long chain fatty acid assays in plasma, red cells, fibroblasts, or amniocytes permit prenatal and postnatal diagnosis and carrier detection. The phenotype of X-linked adrenoleukodystrophy is varied and ranges from the severe and fatal childhood form, to persons who remain asymptomatic in adult life. The underlying biochemical defect is the impaired capacity to degrade very long chain fatty acids, a reaction which normally takes place in the peroxisome. The locus of the adrenoleukodystrophy gene has been mapped to the terminal (Q28) segment of the long arm of the X-chromosome, in close proximity to the loci of Hemophilia A and red-green color blindness. A DNA probe (St14) for this portion of the X-chromosome is of aid for carrier detection. A new dietary regimen, which combines restricted very long chain fatty acid intake with the administration of a glycerol trioleate oil, is capable of reducing plasma very long chain fatty acid levels, and may offer neurological benefit. (j Child Neurol 1987;2:140-150).