ESPE Abstracts

Background: Congenital sodium diarrhea (CSD) is a monogenic disorder caused by specific genetic defects that increase sodium content in the stool, resulting in intractable diarrhea. There are two categories of CSD depending on whether it involves other congenital malformations: non-syndromic congenital sodium loss diarrhea (non-sCSD) and syndromic congenital sodium loss diarrhea (sCSD). For non- sCSD, the identified causative genes include SLC9A3 and GUCY2C, while sCSD is primarily caused by SPINT2 mutations.

Methods: A case of a 7-month-old male with typical diarrhea with fecal sodium and bicarbonate loss who was diagnosed with sCSD and treated in the Second Xiangya Hospital of Central South University in November 2020. Clinical data were collected, including data of genetic sequencing results and clinical manifestations.

Results: Whole-gene exon sequencing revealed a homozygous missense mutation in the 4th exon of the SPINT2 gene in this patient (c.386A>G;p.Y129C), which caused a change in amino acid 129 from Tyr to Cys. We use software simulations of the mutant and wild-type proteins as well as existing knowledge of wild-type SPINT2 and a similar mutant to inform discussion on the consequences of this amino acid change on the structure and function of SPINT2, and how this can manifest clinically as sCSD. We followed the patient until the final outcome, unfortunately, the patient died at the age of 17 months due to severe systemic infection and secondary hemophagocytic syndrome.

Conclusion: Here, we provide evidence for the first time of this novel SPINT2 mutation being involved in the pathogenesis of sCSD as well as the first reported case of sCSD in China. These findings could have implications for genetic counseling for future pregnancies in parents who have children with sCSD.