X-linked adrenoleukodystrophy: Phenotype distribution and expression of ALDP in Spanish kindreds

• Published in: American journal of medical genetics 1998-04, Vol.76 (5), p.424-427
• Main Authors: Ruiz, M., Coll, M.J., Pàmpols, T., Girós, M.
• Format: Article
• Language: English
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenoleukodystrophy - epidemiology; Adrenoleukodystrophy - genetics; Adrenoleukodystrophy - metabolism; adrenoleukodystrophy phenotypes; ALDP; ATP Binding Cassette Transporter, Subfamily D, Member 1; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Endocrinopathies; Female; Gene Expression - genetics; Genetic Linkage; Heterozygote; Humans; Male; Medical sciences; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Non tumoral diseases. Target tissue resistance. Benign neoplasms; peroxisomal disorders; Phenotype; Spain - epidemiology; X Chromosome - genetics
• ISSN: 0148-7299; 1096-8628
• DOI: 10.1002/(SICI)1096-8628(19980413)76:5<424::AID-AJMG11>3.0.CO;2-O

X‐linked adrenoleukodystrophy (X‐ALD) is a neurodegenerative disorder caused by an impairment in peroxisomal β‐oxidation of very long straight‐chain fatty acids (VLCFAs). Six clinical phenotypes have been delineated: childhood cerebral (CCALD), adolescent cerebral (AdolCALD), adult cerebral (ACALD), adrenomyeloneuropathy (AMN), Addison‐only (AO), and presymptomatic (PALD). The distribution of phenotypes varies in different countries. We have diagnosed biochemically 60 X‐ALD Spanish patients belonging to 48 kindreds. Their phenotypic distribution was: CCALD plus AdolCALD, 33%; ACALD, 16%; AMN, 27%; AO, 12%; and PALD, 12%. These results contrast with the distribution described in other countries, due to a higher prevalence of the ACALD form. Regarding the expression of the protein product (ALDP), we studied 17 kindreds using immunochemical techniques and found absence of ALDP in 84% of cases. We also studied 13 females from 7 negative ALDP kindreds in order to correlate ALDP expression and the carrier status established by VLCFA measurement. In one case with normal VLCFA levels in serum and fibroblasts, we observed mosaicism in ALDP expression. This fact supports the use of this technique for identifying carriers. Am. J. Med. Genet. 76:424–427, 1998. © 1998 Wiley‐Liss, Inc.