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California Newborn Screening Program

Phenylketonuria (PKU)

High blood phenylalanine levels are indicative of one of the following categories of disorders in its metabolic pathway: classical PKU, hyperphenylalaninemia, and co-factor variant defect.

Classical PKU is an inherited recessive autosomal disorder (chromosome 12) with an incidence of 1:27,000 in California (1:15,000 in Caucasians, less common in other races). California's lower birth prevalence is due to the preponderance of non-Caucasian births. Since 1966, when PKU screening began, more than 500 cases have been detected.

The disorder is due to a lack of phenylalanine hydroxylase; this is an enzyme needed to metabolize the amino acid phenylalanine to tyrosine (another amino acid); tyrosine is a precursor for such important biochemical products as serotonin, catecholamines, thyroid hormone, and melanin. This enzyme deficiency leads to high levels of phenylalanine and low levels of tyrosine, causing:

  • mental retardation
  • seizures
  • decreased growth rate
  • poor motor skills
  • hypopigmentation

Dietary restriction of phenylalanine (phe), begun within the first few weeks of life, will result in normal development. This is accomplished by replacing most dietary protein with a supplementary formula containing adequate amounts of essential amino acids other than phenylalanine. Phenylalanine can be found in all foods containing protein. By eliminating overtly proteinaceous foods, aspartame (NutraSweet®), and wheat products containing gluten, blood phe levels can be significantly reduced.  Since phenylalanine is an essential amino acid, it should not be totally omitted from the diet: too low a phe level is not healthy, either. The recommended phe-level range is 120 to 360 µmol/L (2 to 6 mg/dl) for children.

Frequent monitoring of the blood phe level and adjustment of the diet is necessary to ensure both adequate nutrition and safe levels of phenylalanine. This strict diet should be followed indefinitely rather than discontinuing it at eight or nine years of age (which was the standard in the past). The current recommendation of diet for life was developed based on studies which indicated that maintaining low phe levels seemed to result in individuals with PKU being able to concentrate better, do better in school, are able to do more complex math problems than when they are not on a low-phe diet.

Severe mental retardation is the rule for individuals with untreated classical PKU. With early adequate treatment, mental retardation is totally preventable. If treatment is delayed for some weeks, the results are more variable. Children who are not treated until after six months of age may show some improvement in IQ, but they will be retarded. Those who are not treated until they are even older usually show little change in IQ, but a phe-restricted diet may help control seizures and/or serious behavioral problems. A mousy or musty odor in older, inadequately treated-individuals is frequently noticed.

Hyperphenylalaninemia (hyperphe) is a term generally used to describe partial enzyme deficiency states in which the level of phenylalanine, while elevated, is lower than in classical PKU, i.e., <600 µmol/L (10 mg/dl). This condition makes up from 35-50% of all cases of persistently elevated levels of phenylalanine picked up by the Newborn Screening Program. The levels may vary in these patients and must be followed periodically.

Information on Cofactor Variants

Parents Guide to PKU (PDF)  

Last modified on: 8/24/2010 3:23 PM