PATHOGENESIS OF X-LINKED ADRENOLEUKODYSTROPHY

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In order to clarify the pathogenesis of X-linked adrenoleukodystrophy (ALD), complementary DNA for human very long chain fatty acyl-CoA synthetase (VLACS), which is deficient in ALD was cloned using rat cDNA.Human VLACS cDNA encodes 620 amino acids with high homology to rat enzyme and fatty acid transport protein and the gene was assinged to chromosome 15q21.2. Polyclonal antibody against human VLACS for protein analysis is raising using purified protein which was expressed by in vitro expression system. Expression vector for human VLACS in cultured human cells is under construction. Carrier identification of ALD was improved by means of plasma very long chain fatty acid (VLCFA) analysis and lignoceric acid oxidation activity in fibroblasts, and the method for the screening of presymptomatic ALD boys was developed. Two novel mutation in ALD protein was identified, and prenatl diagnosis was performed by means of mutation analysis. Incidence of peroxisomal disorders including ALD in Japan was clarified. D-bifunctional protein deficiency, which is characterized by the accumulation of VLCFA,was first identified. As for the peroxisome biogenesis disorders, a novel pathogenic gene (peroxisome assembly factor-2, PAF-2) was identified, screening method using buccal smear was developed, and the treatment with docosahexaenoic acid was investigated. Electroencephalographic characterization of peroxisomal disorders was described.