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Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation
Author(s) -
ToFigueras J.,
Badenas C.,
Carrera C.,
Muñoz C.,
Milá M.,
Lecha M.,
Herrero C.
Publication year - 2006
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-006-0344-6
Subject(s) - acute intermittent porphyria , penetrance , porphobilinogen deaminase , medicine , asymptomatic , porphyria , mutation , asymptomatic carrier , gastroenterology , genotype , urinary system , porphobilinogen , excretion , gene mutation , urine , genetics , endocrinology , biology , gene , phenotype
Summary 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.