The Genetic Landscape and Epidemiology of Phenylketonuria

American Journal of Human Genetics
Alicia HillertNenad Blau

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]...Continue Reading

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Citations

Feb 14, 2021·Metabolic Brain Disease·Vanessa Trindade BortoluzziClovis Milton Duval Wannmacher
Mar 7, 2021·Nutrients·Ella NewbouldAnita MacDonald
Apr 4, 2021·International Journal of Neonatal Screening·Shino OdagiriTakashi Hamazaki
Apr 14, 2021·Orphanet Journal of Rare Diseases·Eva M M Hoytema van KonijnenburgClara D M van Karnebeek
May 22, 2021·Nature Reviews. Disease Primers·Francjan J van SpronsenAnnet M Bosch
Jun 5, 2021·Orphanet Journal of Rare Diseases·Pamela K ForemanSarah Landis
Aug 28, 2021·Nutrients·Rodolfo Ramos-ÁlvarezSusan E Waisbren
Oct 2, 2021·Clinical Chemistry·Kısmet ÇıkıYılmaz Yıldız

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