Citrin缺陷病6例临床特征及基因型特点

摘要/Abstract

摘要： 目的探讨Citrin缺陷患儿临床表型及基因突变特征,提高对Citrin缺陷病的认识。方法回顾性分析厦门市儿童医院确诊的6例Citrin缺陷病患儿的病史资料、实验室检查结果、治疗随访资料。结果 6例患儿中5例因新生儿胆汁淤积就诊,初诊年龄为1 m 7 d～4 m,TBil为(141.3～231.3) μmol/L,DBil为(41.5～94.9) μmol/L,GGT为(133～313) U/L,TBA为(227.3～407.8) μmol/L均明显升高,DBil/TBil＞20% ,AST为(49～148)U/L＞ALT为(10～41)U/L,AFP为(＞3 000～15 000)ng/mL均明显升高。伴低血糖(2.31～3.5)mmol/L 、总蛋白(39.7～60.4)g/L、贫血(90～109)g/L、PT(11.2～23.5)s等,血串联质谱示高瓜氨酸血症。尿质谱示4-羟基苯乳酸、4-羟基苯丙酸、4-羟基苯乙酸升高;5例患儿应用强化中链脂肪酸无乳糖奶粉,熊去氧胆酸及补充脂溶性维生素治疗1～2月后黄疸消退、转氨酶恢复正常,随访患儿体重及身高均在正常范围。1例患儿因发现总胆汁酸升高7年余,晨起低血糖晕厥2次就诊。患儿有喜食高蛋白和高脂肪食物的饮食偏好。6例患儿行全外显子基因检测,分析发现5种SLC25A13 基因突变,c.852-855del为常见突变基因。例6基因检测到SLC25A13基因突变和SLC10A1基因突变,最终诊断为Citrin缺陷病和NTCP基因缺陷病。患儿正通过饮食治疗及随访中。结论 Citrin缺陷病临床表现具有多样性,除新生儿期的胆汁淤积症应警惕Citrin缺陷病外,不明原因的低血糖晕厥及高蛋白质饮食偏爱的患儿也应警惕 Citrin缺陷。及早完善血尿串联质谱及基因检查可帮助明确诊断;及早精准管理患者可有效改善患者预后。

关键词: Citrin缺陷病, 临床特征, 基因型

Abstract: Objective To investigate the clinical characteristics and gene mutation of children with Citrin defect.Methods The data including medical history,laboratory examination,gene mutations and treatment of 6 children with Citrin deficiency diagnosed in Xiamen Children's Hospital were retrospectively analyzed.Results Among the six cases,5 of them were admitted to hospital due to cholestasis and delayed development.The age of the cases ranged from 1m7d to 4m.Biochemical results showed that total bilirubin (141.3～231.3 μmol/L) and conjugated bilirubin (41.5～94.9 μmol/L) were increased,AST(49～148 U/L)＞ALT(10～41 U/L),hypoglycemia(2.31～3.5 mmol/L),hypoproteinemia(39.7～60.4 g/L),blood coagulation abnormality(PT 11.2～23.5s). The alpha fetoprotein were significantly increased(＞3 000～15 000 ng/mL),and blood tandem mass spectrometry showed that hyper citrullinemia.Urine mass spectrometry showed that 4-hydroxyphenyllactate,4-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid were increased.Five children were treated with lactose free fortified medium chain fatty acid milk powder,ursodeoxycholic acid and fat soluble vitamins for 1-2 months,and jaundice subsided.One child was hospitalized because of the increase of total bile acid for more than 7 years,and had hypoglycemic syncope twice in the morning.Children have special dietary preferences,like high protein and high fat food.Six cases of children underwent full exome gene detection,and analysis revealed five of them with SLC25A13 gene mutations.C.852-855del was a common mutation.In case 6,the SLC25A13 gene mutation and the SLC10A1 gene mutation were detected,and the final diagnosis was Citrin deficiency and NTCP gene deficiency.The child is undergoing dietary treatment and follow-up.Conclusion The clinical manifestations of Citrin deficiency are diverse.In addition to cholestasis in the neonatal period,children with unexplained hypoglycemic syncope and a special diet preference to protein-rich foods should also be alert to Citrin deficiency.Early improvement of hematuria tandem mass spectrometry and genetic testing can help to confirm the diagnosis.Early and accurate management of patients can effectively improve the prognosis of patients.

Key words: Citrin deficiency, Clinical characteristics, genotype

王彩红, 卓志强, 黄冰清, 唐文涛, 谢新宝. Citrin缺陷病6例临床特征及基因型特点[J]. 肝脏, 2020, 25(11): 1223-1226.

WANG Cai-hong, ZHUO Zhi-qiang, HUANG Bing-qing, TANG Weng-tao, XIE Xin-bao. Clinical and genotypic characteristics of 6 patients with Citrin deficiency[J]. Chinese Hepatolgy, 2020, 25(11): 1223-1226.

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