1. Background

• CPS is the first enzyme in the urea cycle
• a mitochondrial enzyme, CPS catalyzes the conversion of ammonia and bicarbonate to carbamoyl phosphate
• this reaction is ATP- and magnesium-dependent
• deficiency of N-acetylglutamate Synthestase (an enzyme for the cofactor of this enzymatic reaction) can produce a disorder mimicking CPS Deficiency

2. Genetic Disorder

• genetic disorder -> deficiency of CPS activity -> accumulation of ammonia in the blood and brain (where ammonia acts as a neurotoxin)
• there may be complete and partial deficiencies of CPS activity, the latter characterized by recurrent episodes triggered by sudden protein loads or intercurrent infections

1. Complete CPS Deficiency

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

2. Partial CPS Deficiency

• onset in childhood characterized by recurrent episodes of:

1. Serum

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

2. Urine

• low orotic acid (distinguishes from OTC Deficiency)

3. Diagnosis

• deficiency of CPS 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 hyper-ammonemia 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 hyper-ammonemic coma and morbidity (mental retardation, developmental delays, cortical atrophy)
• good prognosis if disorder is treated prospectively from birth