Phenylketonuria-PKU
Phenylketonuria (PKU) and its milder variant, hyperphenylalaninemia (HPA), are clinical presentations of an autosomal recessive amino acid metabolism disorder caused by defects in the phenylalanine hydroxylase (PAH) gene. More than 500 PAH mutations are known.
PrintPhenylketonuria (PKU) and its milder variant, hyperphenylalaninemia (HPA), are clinical presentations of an autosomal recessive amino acid metabolism disorder caused by defects in the phenylalanine hydroxylase (PAH) gene. More than 500 PAH mutations are known.
Genetic testing is useful in determining carrier status of at-risk relatives and for screening reproductive partners of affected individuals.
The Ambry Test: Phenylketonuria-PKU is a full Gene Sequence Analysis of the PAH gene. Ranges are extended for exons 9 and 10 to detect known splice site mutations. The Ambry Test has a clinical detection rate of >97%.
Phenylketonuria (PKU) and its milder variant, hyperphenylalaninemia (HPA), are clinical presentations of an autosomal recessive amino acid metabolism disorder caused by defects in the phenylalanine hydroxylase (PAH) gene. More than 500 PAH mutations are known. PKU and HPA are most frequent in Caucasians, with a carrier rate of 1/501 and an estimated incidence of 1/10,000-1/15,000 individuals.2
Deficiency of the PAH enzyme leads to elevated blood levels of phenylalanine with potentially toxic neurologic, psychologic, and physiologic effects. Long-term untreated PKU in its most severe form is associated with mental retardation, growth failure, microcephaly, seizures, eczema, hypopigmentation, and tremor. Poorly managed PKU in childhood and adolescence may lead to mood disturbance or cognitive decline. Newborn screening and dietary restriction of phenylalanine intake are effective in preventing most complications of PKU.1,2
Genetic testing is useful in determining carrier status of at-risk relatives and for screening reproductive partners of affected individuals. Testing to identify mutations in affected individuals may suggest the level of intervention needed based on mutation severity3 and response to BH4 (tetrahydrobiopterin, a cofactor of the PAH enzyme).
The Ambry Test: Phenylketonuria-PKU is a full gene analysis performed by PCR-based double-stranded automated sequencing in the sense and antisense directions for exons 1-13 of the PAH gene, plus at least 20 bases into the 5’ and 3’ ends of all the introns. Ranges are extended for exons 9 and 10 to detect known splice site mutations. Specific mutation analysis for individual PAH mutations known to be in the family is also available.
The Ambry Test: Phenylketonuria-PKU has a clinical detection rate of >97%.5,6 Rare gross deletions within the PAH gene are not routinely detected. About 2% of hyperphenylalaninemia (HPA) cases are caused by defects in BH4 metabolism rather than PAH deficiency. HPA caused by BH4 deficiency is not diagnosed by the Ambry Test: Phenylketonuria-PKU.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 μg in TE at 50-100 ng/μl. Store frozen and ship on ice or dry ice.
Prenatal: Prenatal testing is available. Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 1760 | PAH Gene Sequence Analysis | 83891x1, 83894x14, 83898x13, 83904x21, 83909x21, 83912x1 |
| Technique | Days |
|---|---|
| PAH Gene Sequence Analysis | 10-21 |
1 Scriver CR. Hum Mutat. 2007;28:831-845.
2 Williams RA et al. Clin Biochem Rev. 2008;29:31-41.
3 Guttler F, Guldberg P. Eur J Pediatr. 2000:159[Supp.2]:S150-S153.
4 Zurfluh ML et al. Hum Mutat. 2008;29:167-175. Note: Additional phenotype information about mutations may be available at the BIOPKU Database (http://bh4.org/BH4DatabasesBiopku.asp) and the PAHdb Mutation Search (http://www.pahdb.mcgill.ca/).
5 Kozak L et al. Mol Genet Metab. 2006;89:300-309.
6 Phenylalanine Hydroxylase Locus Knowledgebase. Available at: www.pahdb.mcgill.ca/. Accessed August 1, 2008.