Peroxisomal disorders are an extremely heterogeneous group of genetic disorders without strict correlation between clinical picture and biochemical abnormalities. The natural history of the disease course is known to be unpredictable. The analysis of VLCFAs in plasma is necessary as the first screening test for diagnosis of XALD. Sequence analysis (Figure 1) of the ABCD1 mutant allele in the proband revealed a novel point mutation 1519 (G>A) in exon 6, causing the change of glycine at position 507 into serine (G507S). So far, no established correlation between genotype and phenotype has been reported (4). The range of phenotypic expression in XALD and the prognosis for an affected male are unpredictably variable and cannot be predicted through levels of VLCFA in plas ma or cultured skin fibroblasts, the residual VLCFA β-oxidation activity present in XALD skin fibroblasts, the family history or the nature of the mutation identified in the ABCD1 gene of the patient (5). The same mutation can be associated with each of the known clinical phenotypes. The affected boy had developed neurological symptoms and Addison’s disease at 6 years old and a bone marrow transplant at age of 8 without any effect. This mutation in exon 6 caused the changes in the intracellular domain of ALDP and may lead to instability or loss of function of ALDP resulting in accumulation of VLCFAs. Further investigation of ALDP stability in this patient is needed to clarify the impact of this ABCD1 mutation. The childhood cerebral form of XALD is a severe metabolic disease without a definite effective therapy. Mutations in the ABCD1 gene have been identified in the majority of XALD patients, and almost 60% of mutations are non recurrent. In conclusion, analyses of mutations in patients with XALD is necessary, especially for carrier diagnosis and genetic counseling, since more than 900 different mutations in the gene have been reported.

Figure 1. Partial sequence determination of the 1519 (G>A) point mutation of the ABCD1 gene for the hemizy gous proband.