- Autosomal recessive. Incidence ≈ 1:10,000.
- Pathophysiology
- ↓ phenylalanine hydroxylase or
- ↓ tetrahydrobiopterin (BH4) cofactor (malignant PKU): ↑ tryptophan & ↓ serotonin → neurologic deterioration.
- See Catecholamine synthesis
- ↑ phenylalanine → Phenylalanine transaminated to phenyl pyruvic acid, or decarboxylated to phenylethylamine, disrupts normal metabolism & causes brain damage; also produces excess phenyl ketones in urine.
- Phenyl ketones—phenylacetate, phenyllactate, and phenylpyruvate.
- PKU patients must avoid the artificial sweetener aspartame, which contains phenylalanine.
- Findings:
- Normal at birth, followed by gradual intellectual disability, growth retardation
- Infant: severe vomiting, hypertonicity, hyperactive DTRs, seizures
- Older: hyperactive with purposeless movements, rhythmic rocking & athetosis
- Fair complexion, eczema
- Disorder of aromatic amino acid metabolism → musty body odor.
- Maternal PKU—lack of proper dietary therapy during pregnancy. Findings in infant: microcephaly, intellectual disability, growth retardation, congenital heart defects.
- Treatment: ↓ phenylalanine and ↑ tyrosine (becomes essential) in diet, tetrahydrobiopterin supplementation.
- Screening: 2–3 days after birth (normal at birth because of maternal enzyme during fetal life).