Çağan Appak Yeliz, Aksoy Betül, Özyılmaz Berk, Özdemir Taha Reşid, Baran Maşallah
İzmir Katip Çelebi University, Departments of Pediatric Gastroenterology, Hepatology, and Nutrition, İzmir, Turkey.
SBU Tepecik Training and Research Hospital, Departments of Pediatric Gastroenterology, Hepatology, and Nutrition, İzmir, Turkey.
Turk Arch Pediatr. 2022 May;57(3):295-299. doi: 10.5152/TurkArchPediatr.2022.21291.
Gilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome.
Patients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis.
A total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected.
We detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler-Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.
吉尔伯特综合征(GS)是一种因尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)基因启动子突变导致血清间接胆红素水平轻度升高的疾病,该突变会引起尿苷二磷酸葡萄糖醛酸转移酶活性降低。在鉴别诊断中,应根据临床和实验室检查结果考虑吉尔伯特综合征,基因分析可提供支持。本研究旨在评估吉尔伯特综合征患儿的临床特征及UGT1A1基因突变情况。
纳入儿科胃肠病门诊收治的、根据临床和实验室检查结果被认为患有吉尔伯特综合征的患者。采用桑格测序法进行UGT1A1分析。
本研究共纳入56例患儿。分别在75.5%、22.5%和2%的患者中检测到A(TA)7TAA、A(TA)6TAA和(TA)6/7等位基因启动子多态性。除此之外,在3例患者中检测到与GS相关的3种不同序列变异[c.880_893delinsA(p.Tyr294MetfsTer69)和c.1091C>T(p.Pro365Leu)]。
我们在大多数患者中检测到7个TA重复序列。在被认为对吉尔伯特综合征无风险的6次重复序列的病例中,确定有轻度胆红素升高。我们得出结论,先前显示与I型克里格勒 - 纳贾尔综合征相关的c.880_893delinsA(p.Tyr294MetfsTer69)变异,也可能与导致吉尔伯特综合征表型的部分酶缺乏有关。