2019 Volume 248 Issue 1 Pages 57-61
Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Although the etiology of ICP is not fully understood thus far, some genetic factors might contribute to the development of this condition. Sodium-taurocholate cotransporting polypeptide (NTCP), the protein encoded by the gene Solute Carrier Family 10, Member 1 (SLC10A1), is the primary transporter expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile salts from the plasma. NTCP deficiency arises from biallelic SLC10A1 mutations which impair the NTCP function and cause intractably elevated levels of total bile acids (TBA) in the plasma (hypercholanemia). In this study, all the SLC10A1 exons and their flanking sequences were analyzed by Sanger sequencing to investigate the etiology for hypercholanemia in two male infants aged 2 and 20 months, respectively, from two unrelated families. As a result, both patients are homozygous for the reported pathogenic variant c.800C>T (p.Ser267Phe) that could impair the NTCP function to uptake bile acids, and the diagnosis of NTCP deficiency was thus made. Their mothers are also homozygotes of the same variant and both had been diagnosed to have ICP in the third trimester, with one of them undergoing cesarean section. The father of the first patient in this paper has the same SLC10A1 genotype c.800C>T/c.800C>T, also exhibiting slight hypercholanemia with a plasma TBA level of 21.5 μmol/L. In conclusion, we suggest that with hypercholanemia being a common laboratory change, NTCP deficiency may be a genetic factor leading to ICP and even cesarean section in clinical practice.