ArticleAmerican journal of human genetics1998
A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.
Article in American journal of human genetics, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 353 citations in OpenAlex.
- Protein substitute for children and adults with phenylketonuria.The Cochrane database of systematic reviews · 2015Pooled it
- Reassessment of phenylalanine tolerance in adults with phenylketonuria is needed as body mass changes.Molecular genetics and metabolism · 2009Trial
- Blood phenylalanine concentrations in patients with PAH-deficient hyperphenylalaninaemia off diet without and with three different single oral doses of tetrahydrobiopterin: assessing responsiveness in a model of statistical process control.Journal of inherited metabolic disease · 2009Trial
- Metabolic phenotypes of phenylketonuria. Kinetic and molecular evaluation of the Blaskovics protein loading test.Journal of inherited metabolic disease · 2009Trial
- Phenylketonuria in adulthood: a collaborative study.Journal of inherited metabolic disease · 2002Trial
- Article
- Mapping the Severity of Phenylalanine Hydroxylase Deficiency.Journal of inherited metabolic disease · 2026Review
- Molecular Genetic and Biochemical Characterization of Hyperphenylalaninemia Based on Expanded Neonatal Screening Data from 2023 to 2024 in the Russian Federation.International journal of molecular sciences · 2026Article
- Two adult sisters with untreated phenylketonuria: Strikingly discordant clinical phenotype.Molecular genetics and metabolism reports · 2026Article
- Proteasomal activity and disease outcome in phenylketonuria patients with a structural SLC7A5 variant.Scientific reports · 2025Article
- The incidence rate and gene mutation characteristics of hyperphenylalaninemia in Yunnan Province, Southwest China.Orphanet journal of rare diseases · 2025Article
- Sapropterin Dihydrochloride Responsiveness in Phenylketonuria: A Case Series Exploring Gaps in Comprehensive Patient Monitoring.Nutrients · 2025Article
- Inherited metabolic disorders: presentation, clinical types, laboratory diagnosis and genetic markers.Orphanet journal of rare diseases · 2025Review
- Metabolomics and Lipidomics Explore Phenotype-Specific Molecular Signatures for Phenylketonuria.International journal of molecular sciences · 2025Article
- Article
- Genetic andFrontiers in genetics · 2025Article
- Delays in Newborn Screening for Phenylketonuria from Birth to Diagnosis and Factors Affecting This.Children (Basel, Switzerland) · 2024Article
- Neurovascular retinal impairment in early-treated adults with phenylketonuria.Frontiers in neurology · 2024Article
- In Silico Structural Protein Evaluation of the Phenylalanine Hydroxylase p.(Tyr77His) Variant Associated with Benign Hyperphenylalaninemia as Identified through Mexican Newborn Screening.Children (Basel, Switzerland) · 2023Article
- Molecular characterization of phenylketonuria patients from the North Region of Brazil: State of Pará.Molecular genetics & genomic medicine · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
Phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) are allelic disorders caused by mutations in the gene encoding phenylalanine hydroxylase (PAH). Previous studies have suggested that the highly variable metabolic phenotypes of PAH deficiency correlate with PAH genotypes. We identified both causative mutations in 686 patients from seven European centers. On the basis of the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. We proposed and tested a simple model for correlation between genotype and phenotypic outcome. The observed phenotype matched the predicted phenotype in 79% of the cases, and in only 5 of 184 patients was the observed phenotype more than one category away from that expected. Among the seven contributing centers, the proportion of patients for whom the observed phenotype did not match the predicted phenotype was 4%-23% (P<.0001), suggesting that differences in methods used for mutation detection or phenotype classification may account for a considerable proportion of genotype-phenotype inconsistencies. Our data indicate that the PAH-mutation genotype is the main determinant of metabolic phenotype in most patients with PAH deficiency. In the present study, the classification of 105 PAH mutations may allow the prediction of the biochemical phenotype in >10,000 genotypes, which may be useful for the management of hyperphenylalaninemia in newborns.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.