title: Adrenoleukodystrophy in Norway: high rate of de novo mutations and age-dependent penetrance.
abstract: To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.
authors: Department of Neurology, Oslo University Hospital, Oslo, Norway. morten.andreas.horn@ous-hf.no
authors: Morten A
authors: MA
authors: Horn
authors: Lars
authors: L
authors: Retterstøl
authors: Michael
authors: M
authors: Abdelnoor
authors: Ola H
authors: OH
authors: Skjeldal
authors: Chantal M E
authors: CM
authors: Tallaksen
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009664:Norway / Q000453:epidemiology; D019683:Penetrance; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters