1. Background

• ASS is the third enzyme in the urea cycle
• catalyzes the conversion of citrulline + aspartic acid to argininosuccinic acid
• this reaction is ATP- and magnesium-dependent

2. Genetic Defect

• genetic defect -> deficiency of ASS activity -> accumulation of ammonia and citrulline
• ammonia is a neurotoxin affecting the CNS
• citrulline accumulates in the blood, urine, and CSF
• there may be complete and partial deficiencies of ASS activity, the latter characterized by recurrent episodes triggered by sudden protein loads or intercurrent infections

1. Complete ASS Deficiency

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

2. Partial ASS 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
  • elevated citrulline (40x normal, >1000 uM)
  • low arginine
  • elevated glutamine, alanine, and lysine

2. Urine

• elevated citrulline

3. Diagnosis

• deficiency of ASS activity in liver samples and in cultured skin fibroblasts
• prenatal
  • deficiency of ASS activity in cultured chorionic villi or amniocytes

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