Fatal Neonatal Citrullinemia Type I Unmasking a History of Recurrent Reproductive Loss in a Non-Consanguineous Indian Family: A Case Report

This case report describes a fatal neonatal presentation of Citrullinemia Type I (CTLN1) in a term male infant from a non-consanguineous Indian family, a diagnosis that eventually provided an explanation for a significant history of recurrent reproductive loss (G6P2A4L0). The neonate initially manifested with refractory hypoglycemia at 10 hours of life, necessitating glucose infusion rates up to 13~mg/kg/min$, before progressing to severe hyperammonemic encephalopathy with a peak ammonia level of 1280~\mu mol/L$. Despite intensive supportive care, the infant died on day 15; however, postmortem tandem mass spectrometry revealed a diagnostic citrulline elevation of 1100~\mu mol/L, and whole exome sequencing identified a homozygous pathogenic splice-site variant in the ASS1 gene (c.421-2A>G). The case underscores the critical need for expedited newborn screening infrastructure in India, as the 20-day turnaround for biochemical results arrived only after the patient’s death, while highlighting how community endogamy can mimic consanguinity to facilitate rare autosomal recessive disorders