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 skin itching.Two children were not treated before the age of 5,1 child before the age of 13 were not treated in time,progressed to cirrhosis.Conclusion 3β-hydroxy-△5-C27-steroid dehydrogenase is the most common bile acid synthetic defects described to date.The clinical presentation of this disorder include neonatal cholestasis,low or normal serum total bile acid concentration and a normal serum γ-GT concentration,bile acid significantly reduced in the bile.Definitive diagnosis can be achieved by gene analysis ; Prompt diagnosis and early treatment are essential,primary bile acid treatment leads to clinical and biochemical control and prevents chronic liver disease.
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