Family evaluations in acute intermittent porphyria using red cell uroporphyrinogen I synthetase.

Abstract

SUMMARY Acute intermittent porphyria (AIP) is a primary disorder of haem biosynthesis that is chemically characterised by raised urinary porphobilinogen (PBG). A defect in the biochemical pathway at the step of PBG conversion to uroporphyrinogen has been shown to be a result of a partial deficiency of the enzyme uroporphyrinogen I synthetase (uro I syn). The (Strand et al., 1970), fibroblasts (Bonkowsky et al., 1975), lymphocytes (Sassa et al., 1977), and peripheral red cells (Magnussen et al., 1974) from patients with AIP.Evaluation of blood relatives of clinically affected AIP individuals using the red cell uro I syn assay revealed a higher rate of latent AIP than would have IPresented in part at the annual meeting of the American Society of Human Genetics, October 1977. Received for publication 19 July 1978 been found using urinary PBG measurement alone. It was the purpose of this study to assess the efficacy of these two diagnostic tests for the identification of latent AIP in an affected kindred. Magnussen et al. (1974). Though an approximate 50 % reduction in the uro I syn 134 on 9 May 2018 by guest. Protected by copyright. Methods

Genetic heterogeneity of the porphobilinogen deaminase gene in Swedish families with acute intermittent porphyria

“…The diagnosis of the disease has mainly been based on the assay of PBG deaminase activity in red blood cells and urinary excretion of PBG or ALA. However, there is an overlap in enzyme activity between carriers and non-carriers (Lamon et al 1979;McColl et al 1982;Kappas et al 1983). Families have been reported in which AIP patients have shown enzyme activities within the normal range in red blood cells (RBC) (Mustajoki 1981;Mustajoki and Tenhunen 1985).…”

Haplotyping of the human porphobilinogen deaminase gene in acute intermittent porphyria by polymerase chain reaction

“…The PBGD activity in red blood cells has been used for this purpose, even though there is a wide range (about threefold) in the activity of this enzyme in healthy individuals. Furthermore, there is some overlap between the values found in noncarriers and AlP patients (Lamon et al 1979;Kappas et al 1983).…”

Linkage disequilibrium between DNA polymorphisms within the porphobilinogen deaminase gene

“…Elder important part of the management of this condition. Accurate identification or exclusion of carrier status is not always possible by conventional biochemical methods (Lamon et al 1979;Bonaiti-Pellie et al 1984;Lee et al 1988;Pierach et al 1987). Three intragenic restriction fragment length polymorphisms (RFLPs) of the human PBG-deaminase gene have now been identified (Llewellyn et al 1987;Lee et al 1988) and their use in identifying gene carriers has been described (Llewellyn et al 1987;Lee et al 1988).…”