Neonatal Acute Liver Failure due to Citrin Deficiency (NALFCD)

Both citrin deficiency (CD) and citrullinemia type I (CTLN1) may be detected by elevated citrulline through newborn screening (NBS) or present as acute liver failure in later infancy, but they differ significantly in management. This may pose therapeutic challenges in the early period after presentation while awaiting diagnostic confirmation. We report a Chinese girl (birth weight 1.98 kg at 37 weeks) who was recalled on day 5 for elevated citrulline (47 μmol/L; cutoff < 25) and citrulline/arginine ratio of 7.34 at NBS on day 2. Citrulline rose to 264 μmol/L upon retesting on day 5. Initial investigations revealed INR of 3.4 and raised alkaline phosphatase, while ammonia, conjugated bilirubin, glucose, albumin, gamma-glutamyl transferase, and transaminases were normal. Suspected CTLN1 led to halting protein intake and starting high glucose infusion. Within 17 h, INR increased to 6.5 and albumin dropped. Worsening hepatic function following high-glucose intake and her small for gestation age status suggested CD. She improved rapidly after switching to lactose-free MCT-enriched formula. Genetic analysis revealed compound heterozygous known pathogenic mutations in the SLC25A13 gene, confirming the diagnosis of CD. This is the first report of CD presenting with neonatal acute liver failure without cholestasis. It highlights the importance of prompt differentiation between CD and CTLN1 in NBS recalls for safe and effective interim treatment.