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 workup
revealed a blood ammonia level of 290 ?mol/L (normal
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.

Jaar van publicatie:2014

Trefwoorden:Encephalopathy, NAGS, Hyperammonemia