Characterization of X-linked adrenoleukodystrophy in different biological specimens from ten Portuguese families

X-linked adrenoleukodystrophy (ALD) is a severe neurodegenerative disease characterized by progressive demyelination, adrenocortical insufficiency and accumulation in tissues and body fluids of unbranched, saturated very long-chain fatty acids (VLCFA). The diagnosis of ALD is usually based on clinical history, neurological examination and the determination of levels of VLCFA in plasma and cultured skin fibroblasts. In the present paper we report the biochemical findings in plasma, cultured skin fibroblasts and lymphoblastoid cell lines from ALD patients. The results obtained indicate that the increment of the ratios C24:0 to C22:0 and C26:0 to C22:0 and of the concentration C26:0 (micrograms/ml) in plasma was parallel with that of fibroblasts, but not with that of Epstein-Barr virus (EBV)-transformed lymphocytes, suggesting that this cell line is not reliable for diagnosis of ALD by VLCFA analysis. Subsequent studies carried out on family members revealed heterozygotes other than obligate carriers and hemizygotes who were pre-symptomatic or had a misdiagnosis of multiple sclerosis or psychosis.