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Hyperphenylalaninemia Clinical Presentation

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


An abnormal newborn screen is the most common history in patients with hyperphenylalaninemia. Infants are screened for elevated phenylalanine in every US state and in Puerto Rico. Several other countries also have established screening programs.

Affected individuals missed by screening may have mild-to-moderate performance deficits, depending on the degree of phenylalanine elevation.

Measurable IQ deficits can be seen at phenylalanine levels in the hyperphenylalaninemia range, particularly as levels reach the teens. At phenylalanine levels near 20 mg/dL, phenylketonuria (PKU)-like symptoms may emerge, including more pronounced developmental abnormalities, eczema, and vomiting. Preliminary evidence indicates milder attention and organizational problems may arise when levels exceed 6 mg/dL.



Most children have few abnormal findings on physical examination.

Some physical stigmata of PKU may be present in individuals who have phenylalanine levels near 20 mg/dL. PKU-like symptoms include eczema and fair hair and skin coloring.



Genetic defects in phenylalanine hydroxylase cause most cases of hyperphenylalaninemia. In a few cases, defective synthesis or recycling of the biopterin cofactor is the cause (see Tetrahydrobiopterin Deficiency).[3]

In some children with mild enzyme deficits, excessive protein intake may elevate phenylalanine levels to a range requiring treatment. The problem may resolve when protein intake is reduced to more ordinary levels. For example, infants with nonphenylketonuric hyperphenylalaninemia who consume excessive infant formula (60-70 oz/d or 1800-2100 mL/d) may demonstrate phenylalanine levels exceeding 10-12 mg/dL. Levels may fall when formula intake is restricted to 32-40 oz/d.

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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