Document Detail


Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation.
MedLine Citation:
PMID:  16817012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
J To-Figueras; C Badenas; C Carrera; C Muñoz; M Milá; M Lecha; C Herrero
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of inherited metabolic disease     Volume:  29     ISSN:  1573-2665     ISO Abbreviation:  J. Inherit. Metab. Dis.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-11-14     Completed Date:  2007-01-08     Revised Date:  2007-03-21    
Medline Journal Info:
Nlm Unique ID:  7910918     Medline TA:  J Inherit Metab Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  580-5     Citation Subset:  IM    
Affiliation:
Biochemistry and Molecular Genetics Unit, Dermatology Unit, Hospital Clínic i Provincial, IDIBAPS, University of Barcelona, Barcelona, Spain. jto@clinic.ub.es
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
DNA Mutational Analysis
Female
Humans
Hydroxymethylbilane Synthase / genetics
Male
Middle Aged
Models, Genetic
Mutation*
Polymorphism, Single-Stranded Conformational
Porphobilinogen / chemistry
Porphyria, Acute Intermittent / genetics*,  metabolism*,  urine
Porphyrins / urine
Sensitivity and Specificity
Chemical
Reg. No./Substance:
0/Porphyrins; 487-90-1/Porphobilinogen; EC 2.5.1.61/Hydroxymethylbilane Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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