Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Spine Surgery, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Endocrinol (Lausanne). 2022 Jul 22;13:898750. doi: 10.3389/fendo.2022.898750. eCollection 2022.
The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis.
Ten NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model.
During the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice.
Both mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.
SLC10A1 基因中的 p.Ser267Phe 突变可导致 NTCP 缺乏。然而，p.Ser267Phe 纯合子个体的完整临床表现及其长期后果仍不清楚。因此，在本研究中，我们对 NTCP 缺乏的表型特征进行了表征，并评估了其长期预后。
招募了 10 名 NTCP p.Ser267Phe 纯合子个体，并进行了全面的医学评估和 5 年的随访观察。还使用 NTCP 全局敲除小鼠模型展示了 NTCP 缺乏的表型特征。
在对 10 名 NTCP p.Ser267Phe 纯合子成年患者进行的 5 年随访观察中，我们发现成人 NTCP 缺乏最常见的表型特征是胆汁淤积、维生素 D 缺乏、骨丢失和胆囊异常。这些个体的血清胆汁酸（BA）谱发生了显著改变，表现为初级和结合型 BA 的比例和浓度均升高。此外，NTCP 缺乏导致血清 BA 水平升高、维生素 D 水平降低，并加重雌激素剥夺诱导的小鼠骨质疏松表型。
NTCP 缺乏的小鼠和人类均表现为胆汁淤积，更容易发生维生素 D 缺乏和加重骨质疏松表型。因此，我们建议在 NTCP 缺乏个体中监测 BA 和维生素 D、骨密度和腹部超声的水平。
