Citrullinemia Type I and Hypertrophic Pyloric Stenosis in a 1-Month Old Male Infant
A 1-month old male infant with CTLN1 presented to the biochemical genetics clinic with 1-week of vomiting and weight loss. The diagnosis of CTLN1 had been made at 4 days of age after he presented with hyperammonemic coma.\nHe was born at term by vaginal delivery to a primigravid Japanese mother and a Caucasian father. Prenatal and family histories were unremarkable. APGAR scores were 8 and 9 and the patient was discharged after 24 h with mild feeding difficulty, which continued at home. At 4 days old, the infant presented with lethargy, hypothermia, seizure, hemodynamic instability and hyperammonemia to greater than 1000 μmol/L. He required prolonged intensive care admission with dialysis and mechanical ventilation. Given high suspicion for urea cycle disorder, the patient was treated with IV sodium phenylacetate, sodium benzoate and L-arginine. During admission, plasma amino acids were consistent with a diagnosis of CTLN1 and newborn screening returned positive with elevated citrulline. Two known mutations for CTLN1 were identified on ASS1 gene sequencing: a heterozygous exon 7 mutation c.421-2A>G and a heterozygous exon 8 mutation c.539G>A (p.Ser180Asn). The infant was discharged home at 17 days of age with proteinrestricted nasogastric tube feeds, L-arginine and sodium phenylbutyrate.\nAt approximately 3 weeks of age, the patient was twice evaluated at an outside hospital for lethargy and emesis. Ammonia level was normal at both visits and labs revealed mild transaminitis and elevated total bilirubin to 3.4 mg/dL. Both times, the infant improved with IV hydration and was discharged home with reflux precautions. However, he was seen 4 days later at the genetics clinic and parents reported non-projectile vomiting for 1 week. Further history revealed that the nasogastric tube had been accidentally removed prior to onset of emesis, and thereafter replaced by parents with reported home nurse confirmation of positioning. In the clinic, the infant was vigorous but diffusely mottled with a weight loss of 0.12 kg in the last 2 weeks. Nasogastric tube placement was again confirmed and the infant was admitted to the inpatient genetics service for further management.\nUpon admission, labs were notable for the following (reference ranges within parentheses): potassium 5.1 mmol/L (3.6-5.5 mmol/L), chloride 100 mmol/L (100-113 mmol/L), bicarbonate 29 mmol/L, (22-26 mmol/L) ALT 44 IU/L (7-35 IU/L), alkaline phosphatase 440 IU/L (50-350 IU/L), total bilirubin 4.3 mg/dL, direct bilirubin 3.4 mg/dL (0.0-0.3 mg/dL). Ammonia level was 59 μmol/L (11-60 μmol/L) and venous blood gas revealed pH 7.45, pCO of 42 mmHg and lactic acid level of 4.1 mmol/L (0.5-2.0 mmol/L). The infant was started on IV dextrose-containing fluids, sodium phenylacetate, sodium benzoate and L-arginine. Sepsis workup with cerebrospinal fluid, blood and urine cultures did not yield a source of infection. Oral challenge without nasogastric tube resulted in continued emesis; therefore, an abdominal ultrasound was obtained. Results revealed hypertrophic pyloric stenosis (HPS) (). Pediatric surgery was consulted and uncomplicated laparoscopic pyloromyotomy was performed on hospital day 2. On post-operative day 4, the infant was discharged home on continuous nasogastric tube feeds and ranitidine for peri-procedural gastritis. The patient has now undergone liver transplant, remains on low-dose L-arginine and is doing well at 11 months of age with age-appropriate neurocognitive parameters.