Phenylketonuria

National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication].Full text

Smith WE, Berry SA, Bloom K, et al. Phenylalanine hydroxylase deficiency diagnosis and management: a 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jan;27(1):101289.Full text  Abstract

1. National Institutes of Health Consensus Development Panel. National Institutes of Health consensus development conference statement: phenylketonuria - screening and management. 2000 [internet publication].Full text

2. Guldberg P, Rey F, Zschocke J, et al. A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype. Am J Hum Genet. 1998;63:71-79. [Erratum in: Am J Hum Genet. 1998;63:1252-53.]Full text  Abstract

3. Elhawary NA, AlJahdali IA, Abumansour IS, et al. Genetic etiology and clinical challenges of phenylketonuria. Hum Genomics. 2022 Jul 19;16(1):22.Full text  Abstract

4. Hillert A, Anikster Y, Belanger-Quintana A, et al. The Genetic Landscape and Epidemiology of Phenylketonuria. Am J Hum Genet. 2020 Aug 6;107(2):234-50.Full text  Abstract

5. Kaye CI, Accurso F; Committee on Genetics, et al. Newborn screening fact sheets. Pediatrics. 2006 Sep;118(3):e934-63.Full text  Abstract

6. Berry SA, Brown C, Grant M, et al. Newborn screening 50 years later: access issues faced by adults with PKU. Genet Med. 2013 Aug;15(8):591-9.Full text  Abstract

7. Arnold G, Vockley J. Phenylalanine Hydroxylase Deficiency. 2000 Jan 10 [updated 2025 Mar 13]. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.Full text

8. Burton BK, Adams DJ, Grange DK, et al. Tetrahydrobiopterin therapy for phenylketonuria in infants and young children. J Pediatr. 2011 Mar;158(3):410-5. Abstract

9. Smith WE, Berry SA, Bloom K, et al. Phenylalanine hydroxylase deficiency diagnosis and management: a 2023 evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2025 Jan;27(1):101289.Full text  Abstract

10. Burton BK, Hermida Á, Bélanger-Quintana A, et al. Management of early treated adolescents and young adults with phenylketonuria: development of international consensus recommendations using a modified Delphi approach. Mol Genet Metab. 2022 Sep-Oct;137(1-2):114-26.Full text  Abstract

11. Burton BK, Grange DK, Milanowski A, et al. The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label screening study. J Inherit Metab Dis. 2007 Oct;30(5):700-7. Abstract

12. Mitchell JJ, Trakadis YJ, Scriver CR. Phenylalanine hydroxylase deficiency. Genet Med. 2011 Aug;13(8):697-707.Full text  Abstract

13. Fiege B, Blau N. Assessment of tetrahydrobiopterin (BH4) responsiveness in phenylketonuria. J Pediatr. 2007 Jun;150(6):627-30. Abstract

14. Enns GM, Koch R, Brumm V, et al. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab. 2010 Oct-Nov;101(2-3):99-109. Abstract

15. Levy H, Burton B, Cederbaum S, et al. Recommendations for evaluation of responsiveness to tetrahydrobiopterin (BH4) in phenylketonuria and its use in treatment. Mol Genet Metab. 2007 Dec;92(4):287-91. Abstract

16. Blau N, Thony B, Cotton RG, et al. Disorders of tetrahydrobiopterin and related biogenic amines. In: Scriver CR, Beaudet AL, Sly SW, et al, eds; Childs B, Kinzler KW, Vogelstein B, assoc eds. The metabolic and molecular bases of inherited disease. 8th ed. New York, NY: McGraw-Hill; 2001:1725-76.

17. van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017 Oct 12;12(1):162.Full text  Abstract

18.  American ​College of Obstetricians and Gynocologists. Practice bulletin no. 802: management of women with phenylalanine hydroxylase deficiency (phenylketonuria). Apr 2020 [internet publication].

19. Sarkissian CN, Gamez A, Wang L, et al. Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20894-9.Full text  Abstract

20. Hydery T, Coppenrath VA. A comprehensive review of pegvaliase, an enzyme substitution therapy for the treatment of phenylketonuria. Drug Target Insights. 2019;13:1177392819857089.Full text  Abstract

21. Pietz J, Kreis R, Rupp A, et al. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. J Clin Invest. 1999 Apr;103(8):1169-78.Full text  Abstract

22. Matalon R, Michals-Matalon K, Bhatia G, et al. Double blind placebo control trial of large neutral amino acids in treatment of PKU: effect on blood phenylalanine. J Inherit Metab Dis. 2007 Apr;30(2):153-8. Abstract

23. Somaraju UR, Merrin M. Sapropterin dihydrochloride for phenylketonuria. Cochrane Database Syst Rev. 2015;(3):CD008005.Full text  Abstract

24. Martinez M, Harding CO, Schwank G, et al. State-of-the-art 2023 on gene therapy for phenylketonuria. J Inherit Metab Dis. 2024 Jan;47(1):80-92.Full text  Abstract

25. Pey AL, Ying M, Cremades N, et al. Identification of pharmacological chaperones as potential therapeutic agents to treat phenylketonuria. J Clin Invest. 2008 Aug;118(8):2858-67.Full text  Abstract

26. Muntau AC, Longo N, Ezgu F, et al. Effects of oral sepiapterin on blood Phe concentration in a broad range of patients with phenylketonuria (APHENITY): results of an international, phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2024 Oct 5;404(10460):1333-45. Abstract

27. Christ SE, Huijbregts SC, de Sonneville LM, et al. Executive function in early-treated phenylketounuria: profile and underlying mechanisms. Mol Genet Metab. 2010;99(suppl 1):S22-32. Abstract

28. Arnold G, Vladutiu CJ, Orlowski CC, et al. Prevalence of stimulant use for attentional dysfunction in children with phenylketonuria. J Inherit Metab Dis. 2004;27(2):137-43. Abstract

29. Smith I, Knowles J. Behaviour in early treated phenylketonuria: a systematic review. Eur J Pediatr. 2000 Oct;159(suppl 2):S89-93. Abstract

30. Zeman J, Bayer M, Stepan J. Bone mineral density in patients with phenylketonuria. Acta Paediatr. 1999 Dec;88(12):1348-51. Abstract

31. Lenke RR, Levy HL. Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome of treated and untreated pregnancies. N Engl J Med. 1980 Nov 20;303(21):1202-8. Abstract

32. Prick BW, Hop WC, Duvekot JJ. Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequelae in untreated and treated pregnancies. Am J Clin Nutr. 2012 Feb;95(2):374-82. Abstract

33. Adams AD, Fiesco-Roa MÓ, Wong L, et al. Phenylalanine hydroxylase deficiency treatment and management: a systematic evidence review of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2023 Sep;25(9):100358.Full text  Abstract