Abstract
Adrenoleukodystrophy (ALD) is an X-linked disease characterized by progressive demyelination of the central nervous system (CMS) and adrenal insufficiency. Adrenal insufficiency may occur in boys with ALD who have not yet developed neurological symptoms and even remain the only clinical manifestation ot ALD. However, when the neurologic manifestations associated with demyelination starts, no children escape rapid and severe deterioration leading to death within 2-4 years. The normal oxidation of very long chain fatty (VLCFA)-CoA in ALD patien's fibroblasts suggested that the gene coding for VLCFA-CoA synthetase was a candidate gene for ALD. Using positional cloning, we identified in Xq28 a gene partially deleted in 7% of ALD patients. Candidate exons were used to isolate cDNAs by exon-connection. The predicted protein sequence (745 aa) encode a peroxisomal transporter that may be involved in the import of the VLCFA-CoA synthetase but not the enzyme itself. We have moreover demonstrated that bone-marrow transplantation can correct or stabilize the evolution of the disease in 3 patients with the severe cerebral form. The use of autologous bone marrow after the insertion of a normal gene would circumvent the need for a histocompatible donnor and may provide the most suitable gene therapy approach before attempting to deliver the ALD in the cells of CNS where it is expressed.
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Aubourg, P., Mosser, J., Douar, A. et al. Identification of adrenoleukodystrophy gene and future therapy. Pediatr Res 33 (Suppl 5), S15 (1993). https://doi.org/10.1203/00006450-199305001-00073
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DOI: https://doi.org/10.1203/00006450-199305001-00073