X-linked adrenoleukodystrophy (X-ALD) is caused by a defect in the gene ABCD1, whicb maps to Xq28 and codes for a peroxisomal membrane protein that is a member of the ATP binding cassette transporter superfamily. X-ALD is panethnic and affects approximately 1:20,000 males. This disease characterized by progressive neurologic dysfunction, occasionally associated with adrenal insufficiency. Objectives: To describe the clinical, laboratory and cerebral MRI characteristics of n Vietnamese patients with X-ALD and to identify b mutations of ABCD1 in these cases. Subjects and Methods: Clinical features, biochemical finding and cerebral MRI lesions of 9 cases from 7 unrelated fa miles were studied. Genomic DNA from these patients was extracted ~ using standard procedures from the peripheral blood leukocytes. Mutation analysis of ABCD1 was performed using Polymerase chain reaction (PCR) and DNA direct sequencing. Results: two families had two children with ( X-ALD, the others were unrelated but one case had family history of X-ALD. Endocrinology symptoms of adrenal insufficiency were observed in 8/9 cases
7/9 cases showed neurological symptoms of cerebral ALD or adrenomyeloneuropathy
2/9 cases had only symptoms of chronic adrenal insufficiency and no neurological symptoms until 12 and 5 years of age, respectively. 8/9 cases had serum cortisole and ACTH measured confirmed adrenal insufficiency. 8/8 cases showed increased plasma VLCFA. Neuroimaging studies (cerebral MRI) showed classical posterior pattern in 7 cases who had neurological symptoms and normal pattern in 2 cases without neurological manifestations. The authors identified 6 different mutations of ABCD1 in 7 patients. Of which, four novel mutations [c.1202GT (p.Arg401Trp)
c.1208TA (p.Met403Lys)
IVS8+28-551bp del
and the extent of deletion included between IVS1+505 and IVS2+ 1501, containing whole the exon 2 (4243bp), plus insertion of 79bp from BAP31 and 8bp from unknown origin in this deleted region.] were identified in four unrelated patients with neurological symptoms. The reported mutation c.1628CT (p:Pro543Leu) was identified in two cases (sibling: elder had no. neurological symptoms and younger had progressive neurological disability). The reported mutation c.1553GA (p.Arg518Gln) was found in a boy without neurogical symptoms at 5 years of age. Conclusions: For the first time, mutations in ABCD1 are identified in X-ALD Vietnamese patients. Despite many mutations having been identified in patients with these clinical phenotypes, the genotype-phenotype correlations have not been clarified.