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Hyperphenylalaninemia Treatment & Management

  • Author: Georgianne L Arnold, MD; Chief Editor: Bruce Buehler, MD  more...
Updated: Nov 30, 2015

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 mmol (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]



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.



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 restriction may be indicated. 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.



Do not restrict activities.

Contributor Information and Disclosures

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.

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

Bruce Buehler, MD Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Intellectual and Developmental Disabilities, American College of Medical Genetics and Genomics, American Association for Physician Leadership, American Medical Association, Nebraska Medical Association

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.

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Phenylalanine hydroxylase converts phenylalanine to tyrosine.
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