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 Continue reading »