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

Hong Wang; Sainan Shu; Chen Chen; Zhihua Huang; DaoWen Wang

doi:10.1515/jpem-2014-0278

Article

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

Hong Wang , Sainan Shu , Chen Chen , Zhihua Huang and DaoWen Wang

Published/Copyright: November 6, 2014

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 3-4

Abstract

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.

Keywords: myocardial damage; NICCD; novel mutations; severe manifestations; SLC25A13

Corresponding authors: DaoWen Wang, MD, PhD and Zhihua Huang, MD, Department of Internal Medicine or Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China, Phone: +86 27 83663280, Fax: +86 27 83663280, E-mail: dwwang@tjh.tjmu.edu.cn, zhhuang@tjh.tjmu.edu.cn

Acknowledgments

This study was supported by the National Natural Science Foundation of China (31400661).

Conflict of interest statement: No conflict of interest to report.

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Received: 2014-6-27

Accepted: 2014-9-26

Published Online: 2014-11-6

Published in Print: 2015-3-1

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Articles in the same Issue

https://doi.org/10.1515/jpem-2014-0278

Keywords for this article

myocardial damage; NICCD; novel mutations; severe manifestations; SLC25A13