Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations.

Neonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with conjugated hyperbilirubinemia and multiple aminoacidemias. We report the case of a Chinese female patient with NICCD disease who manifested prominent clinical features. The patient was diagnosed with NICCD based on cholestasis, aminoacidemia, and hypoproteinemia. She exhibited extreme aminoacidemia, coagulation disorders and untypical myocardial damage, which are rare in other NICCD patients genetically confirmed by us. This myocardial damage observed in obstructive jaundice could be caused by both hyperbilirubinemia and redundant blood bile acids. Screening the SLC25A13 gene revealed that this patient was compound heterozygous harboring two novel mutations, the c. 640C>T (p. Gln214X) in exon 7 and the c. 1709_1710insA (p. Ile570fs573X) in exon 16. Both mutations cause a premature stop codon and thereby truncated peptide or nonsense-mediated with loss of natural function accordingly. In conclusion, extremely manifested clinical features, including significant hyperbilirubinemia, multiple aminoacidemia, hypoproteinemia, coagulation disorders, and myocardial damage related to redundant blood bilirubin and bile acids, were observed in a NICCD patients with two novel mutations.