Hyperphenylalaninemia is a medical condition characterized by mildly or strongly elevated concentrations of the amino acid phenylalanine in the blood.

Phenylketonuria (PKU)-like symptoms, including more pronounced developmental defects, skin irritation, and vomiting, may appear when phenylalanine levels are near 20 mg/dL (1200 mol/L).

[citation needed] People with the genotype for PKU are unaffected in utero, because maternal circulation prevents buildup of [phe].

If the mother has the PKU genotype but has been treated so as to be asymptomatic, high levels of [phe] in the maternal blood circulation may affect the non-PKU fetus during gestation.

It has been suggested that the resulting deficit in the CNS neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients.

[5] Hyperphenylalaninemia most is commonly diagnosed by newborn screening and must be distinguished from classic PKU by confirmatory testing at an experienced center.

[6] Confirmation is done by checking for elevated Phe concentration (> 120 μmol/L) and increased Phe/tyrosine ratio (> 3 if tandem mass spectrometry is used) in a blood sample.