Phenylketonuria (PKU)

Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by a defect in a specific protein - an enzyme called phenylalanine hydroxylase (PAH), which converts phenylalanine into another an amino acid called tyrosine. This conversion is a chemical reaction, which takes place in a normal individual. In a child with PKU there is no chemical reaction to convert phenylalanine to tyrosine. This results in a build up of an excessive amount of phenylalanine and toxic metabolites in all parts of the body, including the brain, blood, and urine. These excesses create a chemical imbalance that results in various degrees of mental retardation. If a baby with PKU is found early and treatment started, mental retardation can be prevented. PKU is treated with a special formula and a low protein diet.

Prevalence: 1:15,000 

Analytes Measured: Phenylalanine (Quantitative) 

Reporting Results:

• Normal: < 3.0 mg/dL
  The final newborn screening reports are mailed to the submitter and physician of record.
• Borderline: 3.0-4.9 mg/dL
  Final PKU results are phoned to the physician/health care provider and faxed. Final newborn screening reports are mailed by certified mail to the submitter and physician of record.
• Positive: 5.0 mg/dL or greater
  Final PKU results are phoned to the physician/health care provider and faxed. Final newborn screening reports are mailed by certified mail to the submitter and physician of record. 

Feeding/Timing Effect:
Minimal. A protein feeding of 24 hours or greater is necessary for optimal screening results. The use of quantitative phenylalanine measurements increases the ability to detect PKU earlier in the baby's life than previously used qualitative assays. 

Considerations:
Infants should be screened > 24 hours after breast or commercial formula feeding have begun. Infants confirmed to have significant hyperphenylalaninemia are placed on special PKU formulas and serum phenylalanine levels are monitored frequently. Persistent mild hyperphenylalaninemia may indicate biopterin deficiency.

Avoiding False Positive and False Negative:
False positives may be seen in very sick infants and infants on Total Parenteral Nutrition, goat's milk, or evaporated milk (Pet, Carnation). False negatives may occur in PKU infants who are taken off protein feedings or are screened prior to receiving protein feedings.

Variant Forms of PKU:

1. There are several intermediate forms of hyperphenylalaninemia in which the Phenylalanine levels are moderately elevated (3-20 mg/dL). In these, mental retardation is variable or absent. With or without special diet, medical monitoring of these individuals is indicated.
2. Biopterin deficiency (less than 5% of the patient population): Defects in the production of a co-factor, tetrahydrobiopterin, result in a PKU- like disorder. Although elevation of Phenylalanine is characteristic in these infants, the medical management is different from that for infants with PKU.
3. Maternal PKU (MPKU) and hyperphenylalaninemia: Infants born of mothers with PKU or its variants may have elevated plasma Phenylalanine in the first hours after birth (even though the infant is genetically normal). Women with hyperphenylalaninemia have an increased risk of miscarriage. If Phenylalanine is elevated throughout the pregnancy, surviving infants suffer stunting and mental retardation, microcephaly and congenital heart defects. If the mother begins a medically supervised Phenylalanine restricted diet prior to conception and maintains her PKU levels throughout the pregnancy, fetal loss or damage to the fetus may be minimized or prevented.

Comment: Phenylalanine levels of 3.0 mg/dL or greater require prompt follow up testing to determine if the baby has classical PKU or variant form. It is highly recommended that baby's physician/health care provider contact one of the Metabolic Treatment Centers (see below) for follow up.

Metabolic Treatment Centers:

• St. Louis Children's Hospital 314-454-6093
• Cardinal Glennon Hospital For Children 314-577-5639
• Children's Mercy Hospital 816-234-3290
• University of Missouri 573-884-5192