title: ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.
abstract: X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene, which encodes a peroxisomal ABC half-transporter (ALDP) involved in the import of very long-chain fatty acids (VLCFA) into the peroxisome. The disease is characterized by a striking and unpredictable variation in phenotypic expression. Phenotypes include the rapidly progressive childhood cerebral form (CCALD), the milder adult form, adrenomyeloneuropathy (AMN), and variants without neurologic involvement. There is no apparent correlation between genotype and phenotype. In males, unambiguous diagnosis can be achieved by demonstration of elevated levels of VLCFA in plasma. In 15 to 20% of obligate heterozygotes, however, test results are false-negative. Therefore, mutation analysis is the only reliable method for the identification of heterozygotes. Since most X-ALD kindreds have a unique mutation, a great number of mutations have been identified in the ABCD1 gene in the last seven years. In order to catalog and facilitate the analysis of these mutations, we have established a mutation database for X-ALD ( http://www.x-ald.nl). In this review we report a detailed analysis of all 406 X-ALD mutations currently included in the database. Also, we present 47 novel mutations. In addition, we review the various X-ALD phenotypes, the different diagnostic tools, and the need for extended family screening for the identification of new patients.
authors.affiliation: Department of Clinical Chemistry, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands. s.kemp@amc.uva.nl
authors.forename: S
authors.initials: S
authors.lastname: Kemp
authors.forename: A
authors.initials: A
authors.lastname: Pujol
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: B M
authors.initials: BM
authors.lastname: van Geel
authors.forename: C D
authors.initials: CD
authors.lastname: Boehm
authors.forename: G V
authors.initials: GV
authors.lastname: Raymond
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000175:diagnosis / Q000235:genetics*; D030561:Databases, Nucleic Acid; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters