Although recent data established that a specific very-long-chain fatty acyl-CoA synthetase is defective in X-linked adrenoleukodystrophy (ALD), the ALD gene is still unidentified.
With a newly devised method of high-performance liquid chromatography (HPLC), we scrutinized lipid extraction of very-long-chain fatty acids of cultured skin fibroblasts from obligate (n = 4) and possible (n = 3) carriers for adrenoleukodystrophy (ALD) in order to establish the best method to detect a carrier for the ALD gene.
Pipecolic acid was elevated, often markedly, in most of the patients with NALD but in none of those with X-linked ALD or adrenomyeloneuropathy, or in normal adults and children, or children with cirrhosis or other neurodegenerative disorders.
We suggest that these abnormalities demonstrate the morphological effects of the ALD gene in the CNS and reflect the physiological alteration in the heterozygous females in families with ALD.
This finding suggests that in addition to the X-chromosomal ALD gene an autosomal gene linked to the HLA class II region is involved in the pathogenesis of X-ALD.
The molecular analysis of the ALD gene as done in this study is thus considered to be the first step to further elucidate the pathogenic mechanism of ALD.
Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis.
Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis.
Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis.
The two most common forms of X-linked adrenoleukodystrophy (X-ALD), the childhood cerebral form (CCER) and the adult form, adrenomyeloneuropathy (AMN), arise from the same mutations in the X-ALD gene at Xq28.
The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD.
The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD.
The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD.
From these results, it is concluded that ALDP is indispensable for the function of peroxisomal beta-oxidation, and thus the treatment of ALD may be possible by the supplementation of ALDP.