Clinical Manifestations of Classic Phenylketonuria (PKU).

Severe hyperphenylalaninemia (plasma phenylalanine levels >20 mg/dL), if untreated, invariably results in the development of signs and symptoms of classic PKU, except in rare unpredictable occasions.

Clinical Features:

The affected infant is normal at birth. Mental retardation may develop gradually and may not be evident for the 1st few months. It is usually severe, and most patients require institutional care if the condition remains untreated. Vomiting, sometimes severe enough to be misdiagnosed as pyloric stenosis, may be an early symptom. Older untreated children become hyperactive, with purposeless movements, rhythmic rocking, and athetosis.

Physical Examination:

On physical examination, these infants are lighter in their complexion than unaffected siblings. Some may have a seborrheic or eczematoid rash, which is usually mild and disappears as the child grows older. These children have an unpleasant odor of phenylacetic acid, which has been described as musty or mousey. There are no consistent findings on neurologic examination. Most infants are hypertonic with hyperactive deep tendon reflexes. About 25% of children have seizures, and more than 50% have electroencephalographic abnormalities. Microcephaly, prominent maxilla with widely spaced teeth, enamel hypoplasia, and growth retardation are other common findings in untreated children.

The clinical manifestations of classic PKU are rarely seen in those countries in which neonatal screening programs for the detection of PKU are in effect.

Neonatal Screening for Hyperphenylalaninemia:

Effective and relatively inexpensive methods for mass screening of newborn infants have been developed and are used in the United States and several other countries. The bacterial inhibition assay of Guthrie, which was the 1st method for the purpose, has been replaced by more precise and quantitative methods (fluorometric and tandem mass spectrometry). All these methods require a few drops of blood, which are placed on a filter paper and mailed to a central laboratory for assay. Blood phenylalanine in affected infants with PKU may rise to diagnostic levels as early as 4 hr after birth even in the absence of protein feeding. It is recommended, however, that the blood for screening be obtained in the 1st 24–48 hr of life after feeding protein to reduce the possibility of false negative results, especially in the milder forms of the condition.