{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T11:29:46Z","timestamp":1700393386837},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[1993,7,9]],"date-time":"1993-07-09T00:00:00Z","timestamp":742176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1994,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We examined whether the degree of residual activity from the mutant phenylalanine hydroxylase (PAH) allele affected phenylalanine metabolism in heterozygotes for phenylketonuria (PKU) or non\u2010PKU hyperphenylalaninaemia (HPA). Discriminant analysis was carried out to find the function of fasting plasma concentrations of phenylalanine (PHE) and tyrosine (TYR) that best separated carriers from non\u2010carriers. This function (0.103TYR \u22120.214PHE<jats:sub>CORR<\/jats:sub> \u22124.499) was subsequently used as the dependent variable, with the<jats:italic>in vitro<\/jats:italic> activity of the expressed mutant PAH as the independent variable, in a regression analysis performed on heterozygotes for mutations that had been studied in a eukaryotic cell expression system. This analysis showed a significant correlation (<jats:italic>r<\/jats:italic>=0.40,<jats:italic>n<\/jats:italic>=140,<jats:italic>p<\/jats:italic>&lt;0.001), although there was a wide spread of values within each of the two major groups of carriers and a considerable overlap between the groups. We conclude that the severity of the mutation, as determined by<jats:italic>in vitro<\/jats:italic> expression analysis, in the mutant PAH gene is reflected in the biochemical phenotype of heterozygotes. This result emphasizes the relevance of the cell expression system used for establishing the relative severities of most mutations at the PAH locus. Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter\u2010 or intra\u2010individual variation in phenylalanine metabolism. Fasting plasma concentrations of phenylalanine and tyrosine thus can not be used to predict the severity of the carried PAH mutation in individual PKU or HPA heterozygotes.<\/jats:p>","DOI":"10.1007\/bf00711621","type":"journal-article","created":{"date-parts":[[2004,11,30]],"date-time":"2004-11-30T12:22:34Z","timestamp":1101817354000},"page":"215-222","source":"Crossref","is-referenced-by-count":11,"title":["Severity of mutation in the phenylalanine hydroxylase gene influences phenylalanine metabolism in phenylketonuria and hyperphenylalaninaemia heterozygotes"],"prefix":"10.1002","volume":"17","author":[{"given":"E.","family":"Svensson","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry Huddinge University Hospital  Huddinge S\u2010141 86 Sweden"},{"name":"Division of Molecular and Developmental Biology Samuel Lunenfeld Research Institute, Mount Sinai Hospital  600 University Avenue Toronto M5G 1X5 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Iselius","sequence":"additional","affiliation":[{"name":"Department of Surgery Karolinska Hospital  Box 60500 Stockholm S\u2010104 01 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Hagenfeldt","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Huddinge University Hospital  Huddinge S\u2010141 86 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1993,7,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(73)90069-3"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(73)90070-X"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(73)90380-X"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/327333a0"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(05)80274-5"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380010104"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1974.tb01838.x"},{"key":"e_1_2_1_9_1","first-page":"1","article-title":"Hyperphenylalaninemia: Diagnosis and classification of the various types of phenylalanine hydroxylase deficiency in childhood","volume":"280","author":"G\u00fcttler 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