PKU is inherited in an autosomal recessive pattern. Normally a person has two functional PAH genes. In people with PKU, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with PKU typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Without treatment, children with PKU develop the classic symptoms of intellectual disability, behavior problems, light colored hair, seizures, eczema, a musty body odor and a small head size.
- Incidence and New York State Method of Screening (First Tier): Screening for PKU is accomplished by measuring phenylalanine (phe) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Phenylalanine may be elevated in newborns receiving total parenteral nutrition. False positive results may be caused by an unsuitable newborn screen sample, liver immaturity, protein overload, and possible heterozygosity for PAH deficiency in premature babies. Newborn screening cannot differentiate between tetrahydrobiopterin (BH4) defect, hyperphenylalanemia and classic PKU. A newborn screen sample collected prior to 24 hours of age may be falsely negative in infants with PKU who have not been fed enough protein to have an elevated level of phe.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for PKU are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of PKU.
Diagnostic testing includes blood tests for phenylalanine and tyrosine levels. Urine pterins, a test for BH4 (tetrahydrobiopterin) defect, may also be done to rule out an enzyme cofactor deficiency.
Treatment is typically dietary management, including careful monitoring of protein intake. Most people with PKU need to drink a special formula low in phenylalanine, but containing other essential amino acids. More recently, a medication (sapropterin dihydrochloride) is available as a treatment. In some patients, this medication is used to lower phe levels, usually in combination with a low protein diet.
The symptoms of PKU are completely prevented in people on dietary therapy.
A component of protein (phenylalanine) is broken down as part of normal metabolism. The PAH gene provides instructions for an important enzyme in this process, phenylalanine hydroxylase. If there is a mutation in PAH gene, the enzyme does not function and phenylalanine is not broken down. Toxic metabolites accumulate and cause symptoms.