Medical Care

If available, patients should be evaluated at a phenylketonuria (PKU) treatment center. The extent of the hyperphenylalaninemia determines the nature and frequency of follow-up.^[4]

In one study, 54% of patients with phenylalanine levels less than 600 µmol/L (10 mg/dL) demonstrated a decline of 30% or more in plasma phenylalanine levels when sapropterin (commercial tetrahydrobiopterin cofactor) was administered at a dose of 10 mg/kg/d.^[5]The percentage of patients who responded declined with increasing plasma phenylalanine levels. Response to sapropterin may improve at a dose of 20 mg/kg/d.^[6]

Preliminary studies are underway for injectable phenylalanine ammonium lyase, an enzyme substitute. This shows promise in animal studies as an alternative treatment to control phenylalanine levels.^[7]

Consultations

If dietary treatment is necessary, refer the patient to a dietitian experienced with PKU (usually a member of a PKU treatment team).

Refer families of affected infants to a medical geneticist or genetic counselor to review the inheritance of hyperphenylalaninemia.

Diet

Determine the degree of dietary phenylalanine restriction for each patient based on untreated phenylalanine levels. For more detailed information on a phenylalanine-restricted diet, see Phenylketonuria.

Breastfeeding is usually possible and should not be stopped unless instructed by a local health official or treatment center.

Aspartame should be restricted from diet. Phenylalanine is a primary component of aspartame.

Aspartame may be present in many artificially sweetened substances, including medicines, vitamins, beverages, and foods. A pharmacist can help determine if a medication has a significant amount of aspartame.

The amount of aspartame in a children's vitamin or in a teaspoon of antibiotic may be significant for a child who can tolerate only 200 mg/d of phenylalanine, yet such a dose may be insignificant for a child who can tolerate more than 1000 mg/d.

Stringent phenylalanine-restricted diets have been reported to cause deficiencies of iron, zinc, selenium, and other nutrients and essential amino acids in patients with PKU. The diet requires careful monitoring by a professional trained in PKU management.

Activity

Do not restrict activities.

Prevention

In general, patients should avoid consuming aspartame because phenylalanine is a primary component of aspartame.

Long-Term Monitoring

Phenylalanine levels determine the need for further outpatient care in patients with hyperphenylalaninemia.

Medication

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. [QxMD MEDLINE Link].
Mak CM, Ko CH, Lam CW, et al. Phenylketonuria in Hong Kong Chinese: a call for hyperphenylalaninemia newborn screening in the Special Administrative Region, China. Chin Med J (Engl). 2011 Aug. 124(16):2556-8. [QxMD MEDLINE Link].
Crujeiras V, Aldámiz-Echevarría L, Dalmau J, Vitoria I, Andrade F, Roca I, et al. Vitamin and mineral status in patients with hyperphenylalaninemia. Mol Genet Metab. 2015 Aug. 115 (4):145-50. [QxMD MEDLINE Link].
Ten Hoedt AE, Hollak CE, Boelen CC, et al. "MY PKU": increasing self-management in patients with phenylketonuria. A randomized controlled trial. Orphanet J Rare Dis. 2011 Jun 27. 6:48. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Matalon R, Michals-Matalon K, Koch R, Grady J, Tyring S, Stevens RC. Response of patients with phenylketonuria in the US to tetrahydrobiopterin. Mol Genet Metab. 2005 Dec. 86 Suppl 1:S17-21. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Agostoni C, Verduci E, Massetto N, et al. Long term effects of long chain polyunsaturated fats in hyperphenylalaninemic children. Arch Dis Child. 2003 Jul. 88(7):582-3. [QxMD MEDLINE Link]. [Full Text].
Berlin CM, Levy HL, Hanley WB. Delayed increase in blood phenylalanine concentration in phenylketonuric children initially classified as mild hyperphenylalaninemia. Screening. 1995. 4:35-39.
Diamond A, Prevor MB, Callender G, Druin DP. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monogr Soc Res Child Dev. 1997. 62(4):i-v, 1-208. [QxMD MEDLINE Link].
Fisch RO, Matalon R, Weisberg S, Michals K. Phenylketonuria: current dietary treatment practices in the United States and Canada. J Am Coll Nutr. 1997 Apr. 16(2):147-51. [QxMD MEDLINE Link].
Gassio R, Artuch R, Vilaseca MA, et al. Cognitive functions in classic phenylketonuria and mild hyperphenylalaninaemia: experience in a paediatric population. Dev Med Child Neurol. 2005 Jul. 47(7):443-8. [QxMD MEDLINE Link].
Recommendations on the dietary management of phenylketonuria. Report of Medical Research Council Working Party on Phenylketonuria. Arch Dis Child. 1993 Mar. 68(3):426-7. [QxMD MEDLINE Link]. [Full Text].
Scriver CR, Kaufman S, Eijsensmith RC. The hyperphenylalaninemias. The Metabolic and Molecular Bases of Inherited Disease. 1995. Vol 1: 1015-76.
Procházková D, Jarkovský J, Haňková Z, Konečná P, Benáková H, Vinohradská H, et al. Long-term treatment for hyperphenylalaninemia and phenylketonuria: a risk for nutritional vitamin B12 deficiency?. J Pediatr Endocrinol Metab. 2015 Nov 1. 28 (11-12):1327-32. [QxMD MEDLINE Link].

Media Gallery

Phenylalanine hydroxylase converts phenylalanine to tyrosine.

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Author

Eric T Rush, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Geneticist, Children's Mercy Hospital of Kansas City

Eric T Rush, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical, Biomarin Pharmaceuticals, ObsEva, Inozyme Pharma, Ascendis Pharma<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical, and Biomarin Pharmaceuticals<br/>Received research grant from: Alexion Pharmaceuticals, Ultragenyx Pharmaceuticals.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Christian J Renner, MD Consulting Staff, Department of Pediatrics, University Hospital for Children and Adolescents, Erlangen, Germany

Disclosure: Nothing to disclose.

Georgianne L Arnold, MD Faculty, Department of Pediatrics, Divison of Genetics, University of Pittsburgh School of Medicine

Georgianne L Arnold, MD is a member of the following medical societies: American College of Medical Genetics and Genomics, Society for Inherited Metabolic Disorders, Society for the Study of Inborn Errors of Metabolism, American Society of Human Genetics

Disclosure: Received grant/research funds from Biomarin for clinical trial.