title: Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation.
abstract: Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients.
authors.affiliation: Biochemistry and Molecular Genetics Unit, Dermatology Unit, Hospital Clínic i Provincial, IDIBAPS, University of Barcelona, Barcelona, Spain. jto@clinic.ub.es
authors.forename: J
authors.initials: J
authors.lastname: To-Figueras
authors.forename: C
authors.initials: C
authors.lastname: Badenas
authors.forename: C
authors.initials: C
authors.lastname: Carrera
authors.forename: C
authors.initials: C
authors.lastname: Muñoz
authors.forename: M
authors.initials: M
authors.lastname: Milá
authors.forename: M
authors.initials: M
authors.lastname: Lecha
authors.forename: C
authors.initials: C
authors.lastname: Herrero
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011162:Porphobilinogen / Q000737:chemistry; D017118:Porphyria, Acute Intermittent / Q000235:genetics* / Q000378:metabolism* / Q000652:urine; D011166:Porphyrins / Q000652:urine; D012680:Sensitivity and Specificity
chemical_list: D011166:Porphyrins; D011162:Porphobilinogen; D011163:Hydroxymethylbilane Synthase