A neonatal case of citrullinemia with urolithiasis.

To the Editor: Citrullinemia is a rare autosomal recessive inborn error of urea cycle metabolism caused by a deficiency of argininosuccinate synthetase. At least half of genetically affected newborns present in the first several days of life. Major clinical symptoms and signs of hyperammonemia in the neonatal period are difficulty in feeding, vomiting, tachypnea, lethargy, convulsion and coma. The neonatal forms are serious and many times are associated with a high level of mortality,1 We describe a neonatal case of citrullinemia associated with urolithiasis.

A 2900-g baby showed symptoms of hypotonia, tachypnea and difficulty in feeding on the third day of his routine care in the maternity ward of our clinic after an uneventful vaginal delivery. With these symptoms, the patient was screened for sepsis. All the culture results were negative after 48 hours. On the 4th day, he developed left-sided clonic convulsions. The seizures did not respond to intravenous dormicum (midazolam) and phenytoin. Arterial blood gas analysis was normal. Blood was taken for serum ammonia level and a metabolic screen. Subsequent development of apnea and dilated poorly responsive pupils led to intubation and mechanical ventilation. Laboratory results included severely elevated ammonia (619 mol/L). The citrulline level was extremely elevated by the tandem mass spectrophotometer and the urinary citrulline level was also found to be extremely elevated. No peak belonging to argininosuccinic acid was seen. Quantitative analysis of plasma amino acids revealed citrulline to be 1142 μmol/L (10–45) which was extremely elevated. The patient was treated by hemodialysis and enteral sodium benzoate because of his high ammonia level.

Because citrullinemia can be associated with multiple congenital anomalies and organ disease, an ultrasonographic (US) evaluation of the cranium and abdomen was performed.

Cranial US was normal. The abdominal US revealed calculi at the distal end of the left ureter and right renal pelvis. There was a history of parental consanguinity. The patient was lost on the tenth day of admission to the neonatal intensive care unit due to encephalopathy.

Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia.1 The prognosis depends on early diagnosis, which is based on clinical suspicion and analytical determination of ammonia in every newborn with unexplained vomiting, lethargy or other symptoms of encephalopathy.2

Many anomalies and organ disease have been reported in surviving citrullinemia cases, including transposition of the great arteries, subarachnoid hemorrhage, intracranial anomalies, intrahepatic cholestasis, and cutaneous manifestations are some of the anomalies reported in the literature.1–4 In conclusion we want to emphasize the association of the disease with urolithiasis so that renal calculi are kept in mind in cases who survive.