Schneider A L, Köhler H, Röthlisberger B, Grobholz R, McLin V A
Swiss Pediatric Liver Center, Division of Pediatric Specialties, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland.
Department of Pediatrics, Hospital of Aarau, Switzerland.
Clin Res Hepatol Gastroenterol. 2022 Mar;46(3):101824. doi: 10.1016/j.clinre.2021.101824. Epub 2021 Oct 29.
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.
We describe the findings of a patient with a previously unreported homozygous mutation and review all published cases to date in English on PubMed.
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.
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.
关于肝细胞基底外侧的胆汁酸转运体缺陷，人们了解甚少。2015年，瓦斯等人报道了首例因SLC10A1突变导致牛磺胆酸钠共转运多肽缺乏，伴有高胆汁血症、胆红素及自分泌运动因子水平正常的病例。该索引患者表现为生长发育迟缓，但无瘙痒或黄疸症状。自那以后，又有几例新病例发表，但SLC10A基因突变的完整临床表现谱尚不清楚。本综述的主要目的是报告一名患有新型纯合突变的患者，并结合迄今为止所有其他报道的病例来讨论研究结果。
我们描述了一名患有此前未报道的纯合突变患者的研究结果，并回顾了截至目前在PubMed上以英文发表的所有病例。
我们的女性患者出生于2002年，出现了喂养障碍和生长发育迟缓，与瓦斯首次描述的情况相似。检查提示存在潜在的肝脏疾病，尽管她没有瘙痒症状。血清转氨酶、碱性磷酸酶、γ-谷氨酰转移酶和胆红素水平均正常。血浆胆汁酸长期升高，高达150倍。2岁时进行的首次肝活检显示有非特异性结果，伴有局灶性脂肪变性。开始使用熊去氧胆酸治疗，并定期监测肝功能指标。14岁时进行了第二次活检，组织学检查结果正常。此时，发现血清自分泌运动因子水平在正常范围内。最后，基因分析显示SLC10A1基因存在一个5bp的纯合缺失，导致一个提前的终止密码子，预计会导致牛磺胆酸钠共转运多肽完全丧失功能。迄今为止，其他大多数报道的病例携带c.800C>T（p.Ser267Phe）突变，且无症状。
牛磺胆酸钠共转运多肽缺乏症似乎病程良性，因为大多数患者无症状。许多患者似乎表现为短暂的新生儿黄疸。患者之间观察到总血浆胆汁酸水平存在很大差异；这些差异可能与潜在的基因突变或尚未明确的代偿机制有关。需要更长时间的随访来评估这种新发现的胆汁酸转运遗传性疾病的长期后果。
