Phenylketonuria

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

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

Ordering

273
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81406x1
No
Yes
  • 270.1 Phenylketonuria [PKU], Hyperphenylalaninemia
* For price inquiries please email zebras@genedx.com

References

  1. PAHdb: http://www.pahdb.mcgill.ca
  2. Guldberg, P. et al., A European Multicenter Study of Phenylalanine Hydroxylase Deficiency: Classification of 105 Mutations and a General System for Genotype-Based Prediction of Metabolic Phenotype . Am J Hum Genet. 63: 71-79, 1998