PAH deficiency is a well-characterized, treatable, biochemical disorder which results in dietary intolerance to the essential amino acid phenylalanine. It is the most common inborn error of amino acid metabolism in the Caucasian population with an average incidence of 1 in 10,000. PAH deficiency is a condition with a broad phenotypic spectrum that ranges from classic phenylketonuria (PKU) to mild hyperphenylalaninemia (HPA), depending on phenylalanine levels. Most individuals with untreated classic PKU exhibit severe irreversible intellectual disability. Microcephaly, epilepsy, behavioral problems, eczema, hypopigmentation, decreased myelin formation, and a musty urine odor may also be present. Untreated mild HPA may result in mild symptoms depending on the phenylalanine level. Patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4) deficiency will not be expected to have pathogenic variants in PAH. BH4 deficiency is due to defects in the enzymes involved in the synthesis or regeneration of tetrahydrobiopterin (BH4), a cofactor for phenylalanine hydroxylase enzyme. BH4 deficient hyperphenylalaninemia is a genetically heterogeneous group of disorders caused by variants in genes (GCH1, PTS, QDPR, PCBD1, SPR) of the BH4 pathway.

Tests Available

Forms and Documents

Test Details

  • Confirmation of a biochemical diagnosis
  • Carrier testing for at-risk relatives
  • Risk assessment
  • Prenatal diagnosis in families with an affected child and known mutations


4 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swabs | Extracted DNA

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.


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**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.