Unraveling the complexity: A rare case of urea cycle defect and its clinical implications

Background:  Argininosuccinate lyase deficiency is a rare urea cycle disorder that leads to severe hyperammonemia, particularly in neonates. Early identification and intervention are crucial to prevent neurological damage and improve long-term outcomes.

Case Presentation: This case presentation describes the clinical course of an 18-year-old male from South Africa, who was referred to the Adult Endocrine Unit for further management after being diagnosed with life-threatening hyperammonemia in the neonatal period. Presenting on the fourth day of life, the patient was ventilator-dependent and required peritoneal dialysis. Analytical results obtained during the hyperammonemia crisis showed considerable perturbements of metabolic parameters; potassium was 6.6 mmol/L, urea was <1 mmol/L and the peak ammonia level was 2590 μmol/L. The change in amino acid level showed that glutamine, alanine, and argininosuccinic acid were increased. Molecular genetic testing finally led to the diagnosis of argininosuccinate lyase deficiency, a urea cycle disorder. Mostly, dietary protein intake was restricted to about 1 g/kg/day, and the use of ammonia precursors such as sodium phenylbutyrate and sodium benzoate, L-arginine, and branched-chain amino acid supplementation.               

The patient was treated and developed normally up to puberty, but he had mild neurocognitive delay that affected his school attendance in the mainstream schools. He ended up experiencing multiple hyperammonemia crises in his lifespan and the last admission with crisis in September 2024 ammonia increased to 228 umol/L (11-35umol/L), treated with Dextrose 10%infusion and ammonia scavengers, and protein restriction, ammonia dropped to 93 umol/L within 24 hours.

Conclusion:  This case shows that urea cycle defect requires early diagnosis and continuing treatment to prevent episodes of hyperammonemia crisis. Our patient had normal physical growth but had neurocognitive dysfunction, which is why the management of this rare urea cycle disorder is challenging.