Early treatment of a child with NAGS deficiency using N-carbamyl glutamate results in a normal neurological outcome

Acute hyperammonemia has a variety of etiologies and clinical manifestations. If not treated early in neonates, it leads to irreversible brain damage or death. We present a 7-day-old female patient who was brought to the emergency department with drownsiness and vomiting. Metabolic work-up revealed a blood ammonia level of 290 μmol/L (normal <100 μmol/L in neonates) with a compensated respiratory alkalosis, normal glycaemia and lactate and absence of urinary ketones. Oral feeding was stopped, an infusion of 20 % glucose was started, and sodium benzoate and arginine hydrochloride were given. After a drop of ammonemia within 12 h of treatment, it started rising again. N-carbamylglutamate (NCG) was added resulting in a rapid normalisation of ammonemia. Feedings were progressively reintroduced, the ammonia levels remained low. The results of the metabolic work-up were compatible with carbamyl phosphate synthase 1 (CPS1) or N-acetyl glutamate synthase (NAGS) deficiency. Genetic analysis confirmed the latter diagnosis with a homozygous mutation c. 1450T > C (p.W484R) in exon 6 of the NAGS gene in the patient and a carrier state in both parents. At the age of 9 months, the child is growing well with normal neurological development, under treatment with NCG 100 mg/kg/day and a normal diet. Conclusion: This case highlights the importance of keeping a high index of suspicion and early testing for ammonia levels in neonates/children with unexplained encephalopathy. In neonates with congenital hyperammonemia, NCG should always be started together with the standard management of hyperammonemia until all laboratory investigations are complete or indicate another disease.