Department of Infectious Diseases, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
World J Gastroenterol. 2012 Nov 28;18(44):6504-9. doi: 10.3748/wjg.v18.i44.6504.
Progressive familial intrahepatic cholestasis type 1 is a rare disease that is characterized by low serum γ-glutamyltransferase levels due to mutation in ATP8B1. We present a 23-year-old male who experienced persistent marked pruritus for eighteen years and recurrent jaundice for thirteen years, in addition to cholestasis that eventually became fatal. Genetic sequencing studies of the entire coding (exon) sequences of ATP8B1 and ABCB11 uncovered a novel heterozygous missense 3035G>T mutation (S1012I) and a synonymous 696T>C mutation in ATP8B1. The patient's progression was associated with not only impaired familial intrahepatic cholestasis 1 (FIC1) function but also impaired bile salt export pump expression due to the impaired FIC1 function. Our findings show that patients with intermittent cholestasis can develop progressive liver disease even after several decades and require regular follow up.
进行性家族性肝内胆汁淤积症 1 型是一种罕见疾病，其特征是由于 ATP8B1 突变导致血清 γ-谷氨酰转肽酶水平降低。我们报告了一名 23 岁男性，他经历了 18 年的持续显著瘙痒和 13 年的复发性黄疸，此外还有最终致命的胆汁淤积症。对 ATP8B1 和 ABCB11 的整个编码（外显子）序列进行基因测序研究发现了一种新的杂合错义 3035G>T 突变（S1012I）和 ATP8B1 中的同义 696T>C 突变。该患者的进展不仅与家族性肝内胆汁淤积症 1（FIC1）功能受损有关，还与由于 FIC1 功能受损导致胆汁盐输出泵表达受损有关。我们的发现表明，间歇性胆汁淤积症患者即使在几十年后也可能发展为进行性肝病，需要定期随访。
