Clinical characterization of NTCP deficiency in paediatric patients : A case‐control study based on SLC10A1 genotyping analysis

Abstract

Na+‐taurocholate cotransporting polypeptide deficiency (NTCPD) is a newly described disorder arising from biallelic mutations of the SLC10A1 gene. As a result of a lack of compelling evidence from case‐control studies, its genotypic and phenotypic features remain open for in‐depth investigation. This study aimed to explore the genotypic and clinical phenotypic characteristics of paediatric patients with NTCPD. The SLC10A1 genotypes of all NTCPD patients were confirmed by screening for the prevalent variant c.800C>T and Sanger sequencing when necessary. The clinical presentations and laboratory changes were collected, reviewed and analysed, and then qualitatively and quantitatively compared with the relevant controls. A total of 113 paediatric NTCPD patients were diagnosed while c.374dupG and c.682_683delCT were detected as two novel pathogenic mutations. Hypercholanemia was observed in 99.12% of the patients. Indirect hyperbilirubinemia in affected neonates exhibited higher positive rates in comparison to controls. Moreover, transient cholestatic jaundice, elevated liver enzymes and 25‐hydroxyvitamin D (Vit D) deficiency during early infancy were more commonly observed in patients than in controls. All NTCPD patients exhibited favourable clinical outcomes as a result of symptomatic and supportive treatment. The findings enriched the SLC10A1 mutation spectrum and provided comprehensive insights into the phenotypic characteristics of NTCPD. NTCPD should be considered and SLC10A1 gene should be analysed in patients with above age‐dependent clinical features. Furthermore, over investigation and intervention should be avoided in the management of NTCPD patients.

Genetics: A new clinical tool for the hepatologist

“…Deng et al reported on the clinical characterization of Na‐taurocholate cotransport polypeptide deficiency (NTCPD), a new disorder caused by biallelic SLC10A1 loss‐of‐function variants 14 . The hallmark feature of NTCPD was hypercholanemia and it was frequently associated with indirect hyperbilirubinemia and transient cholestatic jaundice, with elevated liver enzymes and 25‐OH vitamin D deficiency during early infancy.…”

“…However, all patients had favourable outcomes as a result of symptomatic or supportive treatment. Therefore, genetic diagnosis of NTCPD may avoid over‐investigation by invasive approaches and unnecessary treatment 14 …”

Molecular Epidemiology of Na+-Taurocholate Cotransporting Polypeptide Deficiency in Guangdong Province, China: A Pilot Study by Screening for Four Prevalent Variants of the Causative Gene SLC10A1

“…Na + -Taurocholate Cotransporting polypeptide deficiency (NTCPD) is an autosomal recessive disorder affecting the hepatic uptake of bile acids caused by biallelic variants of the solute carrier family 10 member1 ( SLC10A1 ) gene which encodes NTCP protein. The main clinical presentation of this disease is refractory hypercholanemia, transient cholestatic jaundice in infancy, and indirect hyperbilirubinemia in neonates ( Deng et al, 2021 ; Deng, 2021 ). The gene SLC10A1 is located at chromosome 14q24.2, contains five exons and has a total length of 23 kb ( Hagenbuch and Dawson, 2004 ; Shiao et al, 2000 ).…”

“…From June 2015 to September 2021, our team diagnosed 318 NTCPD patients by SLC10A1 gene analysis in China, and the four SLC10A1 variants of c.800C > T (p.Ser267Phe), c.263T > C (p.Ile88Thr), c.595A > C (p.Ser199Arg) and c.665T > C (p.Leu222Ser) were at the top of the list, accounting for 96.3, 2.5, 0.6 and 0.4% of all mutated alleles, respectively ( Deng, 2021 ; Deng et al, 2021 ). In this study, these SLC10A1 variants were screened to investigate the epidemiology of NTCPD in Guangdong, a province with the largest population in China.…”

NTCP: a pharmacological target for multiple liver conditions

“…In conclusion, NTCP is a pharmacological target to prevent entry of hepatitis B and D viruses into hepatocytes, NTCP is a pharmacological target to prolong the postprandial elevation of bile acids resulting in amelioration of hepatosteatosis and NTCP is now with the results of Salhab et al a pharmacological target on activated stellate cells to decrease hepatic fibrosis (figure 1). Since NTCP deficiency appears to be harmless,12 its inhibition is a mechanism of action for drugs worth pursuing.…”