Phenylketonuria (PKU)

This disorder is caused when a baby's body cannot breakdown the amino acid, phenylalanine, which is in protein. PKU is a rare condition due to a recessively inherited deficiency of the enzyme phenylalanine hydroxylase. If the baby is detected by NBS and given a diet low in phenylalanine (very low protein plus a special formula) there will be normal growth and development. Untreated PKU causes severe mental deficiency, which can be avoided if treatment is started in the first weeks of life.

Although severe mental deficiency is usual in untreated cases, occasional asymptomatic adults are found with normal or near normal intelligence. Overall, PKU occurs in about 1 in 10,000 babies born in NSW.

Variant forms of PKU (hyperphenylalaninaemia):

There are several intermediate forms of hyperphenylalaninaemia in which the plasma phenylalanine levels are lower. At present we advocate treatment if phenylalanine levels in the untreated baby are 400 umol/L or more.

In about 1% of cases of high blood phenylalaninaemia, the hyperphenylalaninaemia is caused by enzyme defects of biopterin metabolism. These patients need different treatment. Definitive tests can differentiate these variant forms of PKU. In view of the severity of this group of diseases, all infants with persistently abnormal levels of phenylalanine should be tested by analysis of the Dihydropteridine reductase activity in the blood spot. As well, urine tests for biopterin should be performed at the Biochemistry Department.

Maternal PKU and hyperphenylalaninaemia:

Women with phenylketonuria who are not on a low phenylalanine diet have a very high risk of having a baby with the maternal phenylketonuria syndrome - microcephaly, mental retardation, growth retardation, and in some, congenital heart disease. A phenylalanine-restricted diet before conception and during pregnancy can prevent damage to the foetus. Babies of mothers with untreated PKU have a transient elevation of phenylalanine (200-1000 umol/L) which falls to normal within 24 hours. A screening test for the mothers of infants with transient hyperphenylalaninaemia, particularly if the infant's sample was collected in the first 24 hours after birth, is recommended, as is a screening test for mothers of babies with unexplained microcephaly.

Laboratory tests:

PKU is screened for using Tandem Mass Spectrometry. The normal phenylalanine level of babies in the first week of life is <200 umol/L. Confirmatory testing of elevated results is performed using capillary electrophoresis. Measurement of not only phenylalanine but also tyrosine quantitation allows differentiation of secondary causes of hyperphenylalaninaemia eg due to TPN.

Treatment:

Babies with a blood phenylalanine concentration of 400 umol/L and above are admitted to the Care by Parents ward to determine whether the baby has classical PKU and not a defect of biopterin (BH₄) metabolism. This admission opportunity enables the family to meet the PKU team and be taught the dietary requirements for their baby.

With proper treatment, mental retardation is totally preventable. Treatment should be started as soon after birth as possible in any infant with phenylalanine levels over 400 umol/L, and should be continued preferably for life. Frequent monitoring is required, especially in the first weeks. The expert nutritional supervision required is provided through the PKU clinic.

Screening considerations:

Plasma phenylalanine is not detectably elevated in cord blood. The screening test is almost uniformly abnormal within 48 hours of birth whether or not the baby is receiving full milk feeds.

We know of no missed case of PKU in NSW in the last 25 or more years. However, the earlier the test, the more likely that the phenylalanine level could be in the normal range. Thus, a test before 48 hours of age is deemed inappropriate. When a previous sibling has PKU, however, a test may be performed early provided that if it is negative, a follow-up test is performed at 3-4 days.