儿童遗传代谢性肝病的临床特点及病理诊断价值

Clinical Characteristics and Pathological Diagnostic Value of Inherited Metabolic Liver Disease in Children

摘要: 目的：探讨儿童不同遗传代谢性肝病的临床特点及病理诊断价值。方法：回顾性分析2018年1月至2022年6月重庆医科大学附属儿童医院行超声引导下经皮肝穿刺活检、临床诊断考虑遗传代谢性肝病且具备组织学资料的215例患儿的病因，总结最终诊断为遗传代谢性肝病患儿的临床特点及病理诊断价值。结果：215例中诊断不明67例，非遗传代谢性肝病67例，遗传代谢性肝病81例。64/81例病理学诊断：33例糖原累积症(GSD)、24例肝豆状核变性(WD)、2例脂质代谢障碍性疾病、1例尼曼–匹克病(NPD)、1例Alagille综合征(ALGS)、1例进行性家族性肝内胆汁淤积症(PFIC)、2例病因未明遗传代谢性肝病(IMLD)。不同遗传代谢性肝病的转氨酶有不同程度升高，36例GSD临床表现为肝脏肿大、低血糖、生长发育迟缓、乳酸升高等；34例WD多有血清铜蓝蛋白降低和24小时尿铜升高；2例脂质代谢障碍和1例NPD均表现为肝脏肿大、低血糖和高血脂；3例ALGS表现为不同程度的胆汁淤积；2例PFIC表现为黄染、肝脏肿大、总胆红素和胆汁酸升高；2例病因未明IMLD临床表现与各型IMLD有重叠；1例Citrin蛋白缺乏症临床表现为黄染、胆汁淤积及肝脾大。部分肝病有特征性组织病理改变，如GSD的植物细胞样肝细胞和细胞器边聚现象；WD的肝细胞偶见糖原化核和线粒体改变；脂质代谢障碍的肝细胞肿胀和Kupffer细胞增多；NPD的大量空泡结构，空泡内有髓样小体；ALGS的小胆管缺乏。结论：儿童遗传代谢性肝病可在任意年龄起病，转氨酶升高、生长发育迟缓、肝脾肿大、反复发作的胆汁淤积等是常见的临床表现，光镜结合电镜的组织学检查可以提高儿童遗传代谢性肝病的检出率，但最终的病理诊断或解释需结合患儿的症状和体征、实验室检查、家族史、影像学以及遗传学分析。

Abstract: Objective: To explore the clinical characteristics and pathological diagnostic value of different inherited and metabolic liver diseases in children. Methods: The etiology of 215 children with inherited metabolic liver disease and histopathological data who underwent ultrasound-guided percutaneous liver biopsy in the affiliated Children’s Hospital of Chongqing Medical University from January 2018 to June 2022 were reviewed, to summarize the clinical characteristics and pathological diagnostic value of children with inherited metabolic liver disease. Results: Among the 215 cases, there were 67 cases of unknown diagnosis, 67 cases of non-inherited metabolic liver disease and 81 cases of inherited metabolic liver disease. 64/81 cases of pathological diagnosis: There were 33 cases of glycogen storage diseases (GSD), 24 cases of Wilson’s disease (WD), 2 cases of lipid metabolic disorders, 1 case of Niemann-Pick disease (NPD), 1 case of Alagille syndrome (ALGS), 1 case of progressive familial intrahepatic cholestasis (PFIC) and 2 cases of unknown inherited metabolic liver disease (IMLD). Transaminase in different genetic and metabolic liver diseases increased in varying degrees. 36 cases of GSD showed hepatomegaly, hypoglycemia, growth retardation and increased lactic acid, 34 cases of WD showed decreased serum ceruloplasmin and elevated 24-hour urinary copper, 2 cases of lipid metabolism disorder and 1 case of NPD showed hepatomegaly, hypoglycemia and hyperlipidemia, and 3 cases of ALGS showed different degrees of cholestasis. PFIC showed yellow staining, hepatomegaly, elevated total bilirubin and bile acid in 2 cases. The clinical manifestations of 2 cases with unknown etiology of IMLD overlap with various types of IMLD, and clinical manifestations of yellow staining, cholestasis and hepatosplenomegaly in 1 case of Citrin protein deficiency. Some liver diseases have characteristic histopathological changes, such as edge aggregation of plant cell-like hepatocytes and organelles in GSD, occasional changes of glycogen nuclei and mitochondria in hepatocytes of WD, swelling of hepatocytes with disturbance of lipid metabolism and increase of Kupffer cells, a large number of vacuolar structures of NPD with myeloid bodies in vacuoles, and lack of small bile ducts in ALGS. Conclusion: Children with hereditary and metabolic liver disease can begin at any age. Elevated transaminase, growth retardation, hepatosplenomegaly and recurrent cholestasis are common clinical manifestations. Histological examination of light microscope combined with electron microscope can improve the detection rate of inherited metabolic liver disease in children, but the final pathological diagnosis or explanation should be combined with symptoms and signs, laboratory examination, family history, imaging and genetic analysis.