1. Background

• OTC is the second enzyme in the urea cycle
• a mitochondrial enzyme, OTC catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline

2. Genetic Defect

• genetic defect -> deficiency of OTC activity -> accumulation of ammonia + orotic acid
• ammonia is a neurotoxin affecting the central nervous system (CNS)

1. Hemizygote Males

• usually normal at birth with onset of features 24-72 hours after feeding (protein load) commences:

2. Heterozygote Females

• in 10% of heterozygote females, onset of symptoms in childhood characterized by recurrent episodes of:

1. Serum

• venous hyperammonemia (>500 uM [hemizygotes]; >100 uM [heterozygotes])
• normal anion gap; respiratory alkalosis
• amino acids
  • low citrulline and arginine
  • elevated glutamine and alanine

2. Urine

• high orotic acid (distinguishes from CPS Deficiency)

3. Diagnosis

• deficiency of OTC activity in liver, duodenal, and rectal tissue samples (but not leukocytes or cultured skin fibroblasts)

1. Supportive

• a chronic disease with a life-long risk of episodes of hyperammonemia and thus must:
  • provide long-term follow-up
  • moniter ammonia levels
  • coordinate a multidisciplinary approach:
    • Paediatrics, Neurology, Dietary, Genetics, Metabolics
  • plan for acute episodes

2. Goals of Therapy

• symptomatic control of and avoidance of acute episodes
• not curative

3. Diet

4. Convert Nitrogen to an Excretable Compound

5. Prognosis

• 100% mortality if untreated
• there is a direct correlation between the duration of hyperammonemic coma and morbidity (mental retardation, developmental delays, cortical atrophy)
• good prognosis if disorder is treated prospectively from birth