**Background:** Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene, which encodes the mitochondrial aspartate-glutamate carrier citrin. The condition presents with a spectrum of phenotypes, including neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), intermediate growth disorders with dyslipidemia, and adult-onset citrullinemia type II. NICCD typically manifests in the first 6 months of life with cholestasis, elevated liver enzymes, hypergalactosemia, and characteristic amino acid abnormalities. While many cases resolve spontaneously by 1 year of age, some progress to liver failure or later develop citrullinemia type II. This report presents a rare case of NICCD due to a novel heterozygous deletion of exon 3 of SLC25A13, a mutation not previously described in the literature.
**Methods:** This is a single case report of a male infant born at 39+5 weeks gestation on January 24, 2023, with normal birth parameters (length 49 cm, weight 2.9 kg). He presented with persistent skin yellowing from birth and was admitted to the authors' hospital at 2 months of age (March 20, 2023) due to postnatal skin xanthochromia and elevated transaminases. Clinical evaluation included serial liver function tests, routine blood work, trace element analysis, infectious disease screening, liver and spleen ultrasound, and electrocardiography. Because of persistent symptoms and growth retardation (length 51.5 cm, weight 3.8 kg at 2 months, both −2SD), whole exome sequencing was performed on the patient and his parents at Beijing Children's Hospital on April 6, 2023 (age 2 months 13 days). The variant was classified according to ACMG guidelines.
**Key Results:** Genetic testing revealed a heterozygous deletion of exon 3 of the SLC25A13 gene in the infant, while both parents had no detectable mutations in the gene. The variant was preliminarily judged as pathogenic per ACMG criteria. The patient was diagnosed with citrin deficiency (NICCD). Laboratory findings showed persistent elevation of ALT and AST from birth: ALT ranged from 96 to 114 U/L (reference <50 U/L) and AST from 33 to 94 U/L (reference <40 U/L) over serial measurements from January 26 to April 8, 2023. Total bile acid was elevated initially. However, the patient did not exhibit typical NICCD features such as hypergalactosemia, elevated citrulline, arginine, threonine/serine ratio, or alpha-fetoprotein. Liver and spleen ultrasound at 10 days, 2 months, and 4 months showed no abnormalities (no fatty liver, steatohepatitis, fibrosis, or cirrhosis). Infectious disease workup (hepatitis A-E, syphilis, respiratory syncytial virus, Epstein-Barr virus, Torch virus) was negative. The patient received oral compound glycyrrhizin tablets for 7 days and glutathione pump therapy for 5 days, but ALT did not normalize and even increased to 114 U/L after treatment. By follow-up at 6 months 12 days (August 22, 2023), the skin yellowing had subsided, and liver function had returned to normal without specific treatment. However, growth retardation persisted: length 64 cm (−2SD), weight 7 kg (−2SD). Motor development was delayed (could only raise head at 3 months, lie on side at 4 months, turn over but not sit unassisted at 6 months).
**Clinical Implications:** This case reports a novel heterozygous deletion of exon 3 of SLC25A13 causing citrin deficiency, expanding the known mutational spectrum of the disease. It highlights that NICCD can present with persistent cholestasis and elevated transaminases without the classic metabolic abnormalities (hypergalactosemia, elevated citrulline, arginine, etc.) or imaging findings of fatty liver. The spontaneous resolution of cholestasis and normalization of liver function by 6 months is consistent with the typical transient course of NICCD, but the persistent growth retardation and motor delay underscore the need for long-term follow-up. Clinicians should consider NICCD in the differential diagnosis of neonatal cholestasis, even when typical metabolic markers are absent, and pursue genetic testing when clinical suspicion is high. Early diagnosis can guide nutritional management (e.g., lactose-free, medium-chain triglyceride-enriched formulas) and monitoring for potential progression to adult-onset citrullinemia type II.