Sodium Taurocholate Cotransporting Polypeptide Deficiency Research Articles

Clinical features of sodium taurocholate cotransporting polypeptide deficiency and an analysis of SLC10A1 gene mutation

Clinical features of sodium taurocholate cotransporting polypeptide deficiency and an analysis of SLC10A1 gene mutation

Nursing Care of an Extremely Preterm Infant with Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report

Sodium taurocholate cotransporting polypeptide (NTCP) is a protein encoded by the solute carrier family 10 member 1 gene and expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile acids from the plasma. This study reported an extremely premature infant (EPI) with NTCP deficiency (NTCPD). The patient presented with jaundice, persistently elevated total bile acids, 25-(OH)-VitD deficiency, and cleft palate. Nursing care mainly focused on disease surveillance, jaundice care, nutrition, kangaroo mother care, and psychological care. In response to 5 months of the nursing care, the infant’s weight reached 3.324 kg, the jaundice was alleviated, and the infant gained the ability to suck milk. However, his TBA levels were abnormally elevated, and 25-(OH)-VitD was still deficient when the patient was discharged from hospital. The nurses taught the patient’s parents the importance of monitoring liver function and trace elements during a routine outpatient visit. Telephone follow-up 1 year later showed that the patient was in good health with no obvious clinical manifestations. This article reports our experiences in caring for an EPI with NTCPD. To the best of our knowledge, this is the first case report worldwide in NTCPD nursing care.

Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients.

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.

Increased sulfation of bile acids in mice and human subjects with sodium taurocholate cotransporting polypeptide deficiency

Sodium taurocholate cotransporting polypeptide (NTCP, encoded by Slc10a1/SLC10A1) deficiency can result in hypercholanemia but no obvious symptoms in both mice and humans. However, the consequence of and response to long-term hypercholanemia caused by NTCP deficiency remain largely unexplored. Here, we analyzed lifelong dynamics of serum total bile acid (TBA) levels in Slc10a1-/- mice, and we also assessed changes of TBA levels in 33 young individuals with SLC10A1 loss-of-function variant p.Ser267Phe. We found that overall serum TBA levels tended to decrease gradually with age in both Slc10a1-/- mice and p.Ser267Phe individuals. Liver mRNA profiling revealed notable transcription alterations in hypercholanemic Slc10a1-/- mice, including inhibition of bile acid (BA) synthesis, enhancement of BA detoxification, and altered BA transport. Members of the sulfotransferase (SULT) family showed the most dramatic increases in livers of hypercholanemic Slc10a1-/- mice, and one of their BA sulfates, taurolithocholic acid 3-sulfate, significantly increased. Importantly, consistent with the mouse studies, comprehensive profiling of 58 BA species in sera of p.Ser267Phe individuals revealed a markedly increased level of BA sulfates. Together, our findings indicate that the enhanced BA sulfation is a major mechanism for BA detoxification and elimination in both mice and humans with Slc10a1/SLC10A1 deficiency.

Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency.

The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented. Analysis of the SLC10A1 gene in the patient revealed a homozygous p.Ser267Phe (c.800C>T) variation, which proved to be a single-nucleotide polymorphism (SNP) in the allele frequency of 4.7% of healthy controls. This variation involved a conserved amino acid residue on the orthologous alignment that was predicted to be ‘disease-causing’ by functional analysis using a number of bioinformatic tools. Next generation sequencing was performed; however, no other genetic causes were identified that would affect the bile acid homeostasis in the patient. Moreover, an adult, with the same genotype as the pediatric patient, was identified for the first time as experiencing mild hypercholanemia. The molecular and clinical findings in the present study suggest, for the first time, that there is an association between p.Ser267Phe SNP and hypercholanemia, and this information may be used to clinically identify NTCP deficiency worldwide.