Abstract
X-linked adrenoleukodystrophy (ALD), a leukodystrophy characterized by abnormal accumulation
of saturated very long chain fatty acids in brain white matter and adrenal cortex,
is the most common inherited peroxisomal disorder. The biochemical defect is localized
to the level of lignocer-oyl-CoA synthesis, a step in the peroxisomal β-oxidation
of very long chain fatty acids. The responsible gene encodes a peroxisomal integral
membrane protein of as yet unknown function which is a member of the ATP-binding cassette
transporter protein superfamily. The patient gene mutations are heterogeneously distributed
over the functional protein domains with a tendency to clustering in the nucleotide-binding
fold. The mechanisms by which these mutations cause a loss of protein function is
unknown. Diagnosis of patients and carriers, including prenatal testing, is mainly
based on the clinical picture, the demonstration of increased levels of saturated
very long chain fatty acids in tissues and body fluids as well as on DNA mutation
analyses. There are at least six distinct clinical phenotypes ranging from the severe
childhood cerebral form to asymptomatic persons. The various phenotypes commonly occur
within the same kindred. Modifying genes and/or environmental factors may contribute
to this phenomenon. At present, there is no proven therapy for the prevention or cure
of the neurological disabilities. Several approaches are under investigation including
diets, immunosuppression, bone marrow transplantation and gene therapy.
Key words
Adrenoleukodystrophy - Peroxisomes - Demyelination - ABC transporter - Adrenoleukodystrophy
Gene Mutations - Very long chain fatty acids
