Sodium taurocholate co-transporting polypeptide deficiency

摘要

? 2021 The AuthorsIntroduction: Little is known about bile acid transporter defects on the basolateral side of hepatocytes. In 2015 Vaz et al. published a first case of SLC10A1 mutation causing Na-taurocholate Co-transporting Polypeptide deficiency with hypercholanemia and normal bilirubin and Autotaxin levels. The index patient presented with failure to thrive, but without pruritus or jaundice. Several new cases have been published since, but the full spectrum of clinical presentation of mutations in SLC10A is not known. The primary aim of this review is to report a patient with a novel homozygous mutation and discuss the findings in the light of all other reported cases to date. Material and methods: We describe the findings of a patient with a previously unreported homozygous mutation and review all published cases to date in English on PubMed. Results: Our female patient born in 2002 presented with a feeding disorder and failure to thrive akin to the first description by Vaz. Workup suggested underlying liver disease although she did not complain of pruritus. Serum levels of aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and bilirubin were normal. Plasma bile acids were chronically elevated, up to 150-fold. A first liver biopsy performed at 2 years of age showed unspecific findings with focal steatosis. Ursodeoxycholic acid treatment was introduced and the liver panel monitored regularly. At age 14, a second biopsy was performed, and histology was within normal limits. At this time, serum Autotaxin levels were found to be in normal range. Finally, genetic analysis revealed a homozygous 5 bp deletion in the gene SLC10A1 resulting in a premature stop codon predicted to lead to a complete NTCP loss of function. Most other reported cases to date carry the c.800C>T (p.Ser267Phe) mutation and are asymptomatic. Discussion: NTCP deficiency appears to have a benign course as most patients are asymptomatic. Many patients seem to present with transient neonatal jaundice. Large variations in total plasma bile acid levels are observed between patients; they may be linked to the underlying genetic mutation or to yet uncharacterized compensatory mechanisms. Longer follow-up is needed to evaluate the long-term consequences of this newly identified inherited disease of bile acid transport.