婴儿3β-羟基-△5-C27-类固醇脱氢酶缺陷二例病例报告及文献复习  

Infant with 3β-hydroxy-△5-C27 steroid dehydrogenase deficiency： report of two cases and literatures review

作　　者：李雪松[1] 黄志华[1] 王宏[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿童感染消化科,武汉430030 [2]华中科技大学同济医学院附属同济医院基因诊断中心,武汉430030

出　　处：《中华儿科杂志》2015年第5期360-365,共6页Chinese Journal of Pediatrics

基　　金：卫生部临床重点专科建设项目（小儿消化专科）

摘　　要：目的 探讨婴儿3β-羟基-△5-C27类固醇脱氢酶（3β-HSD）缺陷引起的先天性胆汁酸合成缺陷的临床特点及早期诊断.方法 对2012-2013年武汉同济医院儿科诊断的2例3β-HSD缺陷患儿的临床表现、血生化及肝脏病理特点、基因突变及治疗进行分析总结,并对1993年至今国内外报道53例3β-HSD缺陷患儿的文献进行复习.结果 （1）2例婴儿均生后第3天出现胆汁淤积.院外检查：例1血丙氨酸转氨酶292 U/L,天冬氨酸转氨酶458 U/L,血清胆汁酸1.8 μmol/L,总胆红素125.6 μmol/L,直接胆红素93.8μmol/L,γ-谷氨酰转肽酶（GT）43 U/L,胆汁中胆汁酸17.4 μmol/L.例2血丙氨酸转氨酶812 U/L,天冬氨酸转氨酶819 U/L,血清胆汁酸4.9μmol/L,总胆红素151.3μmol/L,直接胆红素108.8μmol/L,γ-GT 50 U/L,胆汁中胆汁酸66.0 μmol/L.基因检测：例1存在c.130_131insA纯合突变,国内外尚未报道过;例2存在c.544insG/c.790C＞ C/A复合杂合突变.病理结果：2例患儿均有肝细胞内脂滴增多,胆色素颗粒沉积,细胞内糖原颗粒增多,慢性炎性细胞浸润;毛细胆管扩张、胆汁淤积,胆管上皮微绒毛减少.（2）53例通过尿气相色谱质谱分析或快原子轰击质谱分析确诊的患儿资料：33例基因存在HSD3B7突变;多在婴儿期起病,胆汁淤积性黄疸53例,肝肿大22例,脂肪及脂溶性维生素吸收障碍14例;血γ-GT正常或降低53例,血清胆汁酸正常或降低53例;无皮肤瘙痒症状49例;其中2例患儿在5岁之前,1例在13岁前未予及时治疗,进展为肝硬化.结论 3β-HSD缺陷患儿于新生儿期出现胆汁淤积,血清胆汁酸浓度降低或正常,γ-GT值正常,胆汁中胆汁酸明显降低,行基因检测可确诊,及时治疗可改善患儿病情及预后.Objective To study the clinical characteristics and early diagnosis of children with 3β-hydroxy-△5-C27-steroid dehydrogenase （3β-HSD） deficiency.Method Data related to clinical characteristics,serum biochemistry,liver pathology,gene mutations and treatment of two children with 3β-HSD deficiency were analyzed and relevant literature was reviewed.Fifty-three cases of 3β-HSD deficiency were reported since 1993 in the world.Result （1） Both patients showed neonatal cholestasis,blood biochemical examination of patient one showed alanine aminotransferase 292 U/L,aspartate aminotransferase 458 U/L,serum bile acids 1.8 μmol/L,total bilirubin 125.6 μmol/L,direct bilirubin 93.8 μmol/L,γ-glutamyl endopeptidase 43 U/L,bile biochemical test revealed bile acid 17.4 μmol/L,no itching; another patient showed alanine aminotransferase 812 U/L,aspartate aminotransferase 819 U/L,serum bile acids 4.9 μmol/L,total bilirubin 151.3 μmol/L,direct bilirubin 108.8 μmol/L,γ-glutamyl endopeptidase 50 U/L,bile biochemical test revealed bile acid 66.0 μmol/L,there was no itching.Both patients were confirmed by HSD3B7 gene mutation analysis.One patient had a homozygous mutation：130_131insA,a novel mutation had not been reported,the other had compound heterozygous mutations：544insG and 790C 〉 C/A; The electron microscopic findings included bile pigment granules,fat droplets deposited in the cytoplasm of hepatocytes,glycogen granules increased,bile ductular dilatation or proliferation,bile plugs in canaliculus,biliary epithelial microvilli reduced,chronic inflammatory cell infiltration; （2） 53 cases were diagnosed by urine gas chromatography mass spectrometry （GC/MS） or fast atom bombardment mass spectrometry （FAB-MS）,while 33 cases were diagnosed by HSD3B7 gene mutation analysis.All the patients had cholestatic jaundice,22 cases of hepatomegaly,fats and fat-soluble vitamin malabsorption in 14 cases,blood γ-GT normal or decreased in 53 cases,normal or decreased serum bile acid in 53 cases,49 cases had no

关 键 词：胆汁淤积 肝内 代谢缺陷 先天性 婴儿 

分 类 号：R725.9[医药卫生—儿科]