• 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).