Lee Paul, Jones Graham, Seibel Markus J
Department of Endocrinology and Metabolism, Concord Repatriation General Hospital, St Vincent's Hospital, New South Wales, Australia.
Eur J Gastroenterol Hepatol. 2007 Apr;19(4):337-40. doi: 10.1097/MEG.0b013e328012b431.
Gilbert's syndrome is a common inherited disorder, in which genetic defects in uridine diphosphate-glucuronosyltransferase 1A1 lead to deficient glucuronidation of bilirubin and hence hyperbilirubinaemia. Although usually considered asymptomatic, Gilbert's syndrome can be associated with gastrointestinal and psychiatric symptoms unexplained by the metabolic defect. Genetic polymorphism of a closely related enzyme, uridine diphosphate-glucuronosyltransferase 1A6, results in altered metabolism and elimination of serotonin. On the basis of a case of hyperserotoninaemia in the absence of a detectable carcinoid tumour in a patient with Gilbert's syndrome, who presented with a history of night sweats, flushing, abdominal discomfort and intermittent diarrhoea, we propose that in a subgroup of Gilbert's syndrome patients, homozygocity for dual uridine diphosphate-glucuronosyltransferase 1A1 and uridine diphosphate-glucuronosyltransferase 1A6 polymorphisms may lead to combined hyperbilirubinaemia and hyperserotoninaemia. The latter may account for symptoms experienced by patients with Gilbert's syndrome hitherto considered unrelated to, or unexplainable by, the known defect in bilirubin metabolism.
吉尔伯特综合征是一种常见的遗传性疾病，其中尿苷二磷酸葡萄糖醛酸基转移酶1A1的基因缺陷导致胆红素葡萄糖醛酸化不足，进而引起高胆红素血症。尽管通常认为吉尔伯特综合征无症状，但它可能与代谢缺陷无法解释的胃肠道和精神症状相关。一种密切相关的酶——尿苷二磷酸葡萄糖醛酸基转移酶1A6的基因多态性会导致血清素代谢和清除的改变。基于一例吉尔伯特综合征患者出现高血清素血症且未检测到类癌肿瘤的病例，该患者有盗汗、潮红、腹部不适和间歇性腹泻的病史，我们提出在吉尔伯特综合征患者的一个亚组中，尿苷二磷酸葡萄糖醛酸基转移酶1A1和尿苷二磷酸葡萄糖醛酸基转移酶1A6双重基因多态性的纯合性可能导致合并的高胆红素血症和高血清素血症。后者可能解释了吉尔伯特综合征患者迄今被认为与已知胆红素代谢缺陷无关或无法解释的症状。
