Hyperphenylalaninemia Clinical Presentation

Updated: May 18, 2017
  • Author: Eric T Rush, MD, FAAP; Chief Editor: Luis O Rohena, MD, PhD, FAAP, FACMG  more...
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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 exceed 10 mg/dL (600 µmol/L). At phenylalanine levels near 20 mg/dL (1200 µmol/L), 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.