phenylketonuria 2 (dihydropteridine reductase deficiency)

Epidemiology

rare

Pathology

• hyperphenylalaninemia
• signs are attributable to depletion of the neurotransmitters dopamine & serotonin, whose syntheses are controlled by tryptophan hydroxylase & tyrosine hydroxylase that use BH-4 as cofactor

Genetics

• autosomal recessive
• associated with defects in QDPR

Clinical manifestations

• severe neurologic symptoms (malignant hyperphenylalaninemia) including
  • axial hypotonia
  • truncal hypertonia
  • abnormal thermogenesis
  • microcephaly

Laboratory

• dihydropteridine reductase in erythrocytes

Management

• not responsive to phenylalanine-restricted diet
• intravenous tetrahydrobiopterin (BH-4), oral therapy not effective
• lethal if untreated

More general terms

• phenylketonuria (PKU)

Database

• OMIM: https://mirror.omim.org/entry/261630