Ornithine transcarbamylase deficiency (OTC)
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A male newborn becomes lethargic with poor feeding on day 2-3 of life. Ammonia is >1000 μmol/L. He has respiratory alkalosis progressing to coma.
XLR; OTC
- Most common urea cycle disorder
- Males: Neonatal hyperammonemic coma (classic), high mortality
- Females (carriers): Variable - asymptomatic to severe (lyonization)
- Elevated glutamine, low citrulline
- Elevated urinary orotic acid (distinguishes from CPS1 deficiency)
- Not on standard newborn screening; suspected from acute hyperammonemia with respiratory alkalosis
- Plasma amino acids: high glutamine, low citrulline and arginine; urine: elevated orotic acid, low/absent urea cycle intermediates
- Confirmatory: OTC molecular testing (also enables carrier testing in females, where lyonization makes biochemical testing unreliable)
- Protein restriction, nitrogen scavengers (sodium benzoate, phenylbutyrate), liver transplant
OTC = Ornithine To Citrulline: the enzyme converts Ornithine To Citrulline. When OTC is deficient, ornithine and carbamoyl phosphate accumulate.
The "O" in HALO-M: OTC deficiency is the only X-linked urea cycle disorder. HALO-M = Hunter, Adrenoleukodystrophy, Lesch-Nyhan, OTC deficiency, Menkes.
Orotic acid UP, citrulline DOWN: elevated urinary orotic acid (excess carbamoyl phosphate diverts into pyrimidine synthesis) distinguishes OTC deficiency from CPS1 deficiency (which has neither). OTC deficiency presents on "Day One or Two" of life.