Neonatal-onset citrin deficiency: long-term outcomes in four cases and identification of a novel variant.

BACKGROUND

Citrin deficiency (CD), caused by mutations in the SLC25A13 gene, is a rare autosomal recessive urea cycle disorder with variable clinical presentations depending on age. These include neonatal intrahepatic cholestasis (NICCD), failure to thrive with dyslipidemia, and adult-onset type II citrullinemia. Patients with NICCD typically present with transient intrahepatic cholestasis in infancy, which often resolves spontaneously by one year of age; however, some may progress to severe complications later in life.

CASE PRESENTATION

Four cases diagnosed with NICCD phenotype are presented. All patients presented with neonatal cholestasis, hypertransaminasemia, galactosuria, and elevated citrulline levels. Molecular analysis identified three disease-causing variants: two previously reported variants, c.955C>T (p.Arg319*) and c.74C>A (p.Ala25Glu), and a novel variant, c.1359G>T (p.Lys453Asn). Treatment included a galactose-free formula, medium-chain triglycerides, and nutritional supplementation, resulting in biochemical and clinical improvement. All patients in our series exhibited a milder clinical course, with no episodes of hyperammonemia or hypoglycemia, no progression to liver failure, and favorable long-term outcomes with dietary management. During a long-term follow-up period ranging from 7 to 11 years, no severe complications were observed. Notably, one patient developed a recurrence of cataract, emphasizing the importance of lifelong dietary adherence and regular eye examinations.

CONCLUSIONS

The findings in this paper further expand the genotypic spectrum and genotype-phenotype correlations of CD. Lifelong follow-up is recommended, including ocular examination.