ArticleAmerican journal of human genetics2020
The Genetic Landscape and Epidemiology of Phenylketonuria.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
221 citing papers in PubMed, 7 syntheses or guidelines pooled it, 351 citations in OpenAlex.
- Metabolomic profiling in phenylketonuria: a systematic review of human studies.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- The prevalence of phenylketonuria (PKU) and hyperphenylalaninemia (HPA) in Iran: a systematic review and meta-analysis.Orphanet journal of rare diseases · 2026Pooled it
- Intelligence quotient scores among early-treated phenylketonuria patients: results from a systematic literature review.Orphanet journal of rare diseases · 2025Pooled it
- Maternal Phenylketonuria and Offspring Outcome: A Retrospective Study with a Systematic Review of the Literature.Nutrients · 2025Pooled it
- Vitamin Status in Patients with Phenylketonuria: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- Cognitive function in untreated subjects with mild hyperphenylalaninemia: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Pooled it
- Randomized investigation to evaluate phenylalanine fluctuation after overnight fasting in PKU patients treated with prolonged-release versus standard amino acid protein substitute.Orphanet journal of rare diseases · 2026Trial
- Study protocol and pilot study results for a clinical intervention trial of PKU carriers and non-carriers: the Phe for Me trial.Orphanet journal of rare diseases · 2026Trial
- Protein Substitute Absorption: A Randomised Controlled Trial Comparing CGMP vs. Amino Acids vs. Micellar Casein in Healthy Volunteers.Nutrients · 2025Trial
- No QT interval prolongation effect of sepiapterin: a concentration-QTc analysis of pooled data from phase 1 and phase 3 studies in healthy volunteers and patients with phenylketonuria.Journal of pharmacokinetics and pharmacodynamics · 2025Trial
- Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial.Nature metabolism · 2023Trial
- Lower blood phenylalanine concentrations may be of clinical benefit in adults with phenylketonuria.Molecular genetics and metabolism reports · 2026Article
- Amelioration of the neurological phenotype in PKU mouse model emphasizes the potential of base editing for metabolic diseases.Molecular therapy. Advances · 2026Article
- Global Trends in Phenylketonuria Treatment Research, 2000-2025: Bibliometric Analysis.Online journal of public health informatics · 2026Article
- Targeting Mutant Phenylalanine Hydroxylase With Pyrimidine-Triazole Conjugates: A Primary Framework for Candidate Chaperone-Based Strategies in Phenylketonuria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Analysis ofInternational journal of molecular sciences · 2026Article
- Article
- Carnitine, Amino Acids, Vitamins, and Hematological Status in Children with Classical Phenylketonuria: A Case-Control Study.Nutrients · 2026Article
- Sexual and reproductive life in adolescents and young adults with phenylketonuria: a cross-sectional study.Orphanet journal of rare diseases · 2026Article
161 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
48 authors at 20 institutions in 18 countries.
Funding
Abstract
Phenylketonuria (PKU), caused by variants in the phenylalanine hydroxylase (PAH) gene, is the most common autosomal-recessive Mendelian phenotype of amino acid metabolism. We estimated that globally 0.45 million individuals have PKU, with global prevalence 1:23,930 live births (range 1:4,500 [Italy]-1:125,000 [Japan]). Comparing genotypes and metabolic phenotypes from 16,092 affected subjects revealed differences in disease severity in 51 countries from 17 world regions, with the global phenotype distribution of 62% classic PKU, 22% mild PKU, and 16% mild hyperphenylalaninemia. A gradient in genotype and phenotype distribution exists across Europe, from classic PKU in the east to mild PKU in the southwest and mild hyperphenylalaninemia in the south. The c.1241A>G (p.Tyr414Cys)-associated genotype can be traced from Northern to Western Europe, from Sweden via Norway, to Denmark, to the Netherlands. The frequency of classic PKU increases from Europe (56%) via Middle East (71%) to Australia (80%). Of 758 PAH variants, c.1222C>T (p.Arg408Trp) (22.2%), c.1066-11G>A (IVS10-11G>A) (6.4%), and c.782G>A (p.Arg261Gln) (5.5%) were most common and responsible for two prevalent genotypes: p.[Arg408Trp];[Arg408Trp] (11.4%) and c.[1066-11G>A];[1066-11G>A] (2.6%). Most genotypes (73%) were compound heterozygous, 27% were homozygous, and 55% of 3,659 different genotypes occurred in only a single individual. PAH variants were scored using an allelic phenotype value and correlated with pre-treatment blood phenylalanine concentrations (n = 6,115) and tetrahydrobiopterin loading test results (n = 4,381), enabling prediction of both a genotype-based phenotype (88%) and tetrahydrobiopterin responsiveness (83%). This study shows that large genotype databases enable accurate phenotype prediction, allowing appropriate targeting of therapies to optimize clinical outcome.
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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.