Focal glycogenosis of the liver in disorders of ureagenesis: Its occurrence and diagnostic significance
Focal glycogenosis of the liver in disorders of ureagenesis: Its occurrence and diagnostic significance
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DOI：
10.1002/hep.510260217
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发表时间：
1997-08-01
期刊：
影响因子：
13.5
通讯作者：
PerezAtayde, AR
中科院分区：
文献类型：
--
作者：
Badizadegan, K;PerezAtayde, AR
尿素生成代谢紊乱可导致儿童出现Reye样综合征，并伴有潜在致死性高氨血症。这些紊乱的机制异质性亚组共享线粒体瓜氨酸生成受损的生化最终结果，包括线粒体酶、鸟氨酸转氨甲酰酶（OTC）和氨甲酰磷酸合酶（CPS）缺乏，以及二元氨基酸尿症高氨血症-高鸟氨酸血症-高瓜氨酸尿症（I-II-II-I）和赖氨酸尿蛋白不耐受症（LPI）。本文报告了10例尿素生成缺陷患儿的肝脏组织病理学检查，其中6例为OTC缺陷，3例为CPS缺陷，1例为HHH缺陷。肝脏表现为弥漫性微泡性脂肪变性，门静脉周围核糖原明显，门静脉纤维化，偶见门静脉-门静脉桥连。10例患儿中有5例出现散在的扩张肝细胞聚集体，中央核无空泡，胞质透明，其中2例为OTC缺乏症，2例为CPS缺乏症，1例为HHH。以前在一些OTC缺乏症或LPI儿童的肝脏中也观察到类似的聚集物，但其性质和诊断意义迄今仍不清楚。使用特殊染色的冷冻组织切片和电子显微镜，我们发现，在这些聚集体中的肝细胞有很少或没有细胞质中性脂肪，但含有过量的游离细胞质糖原，形态学模仿糖原贮积病。根据我们的经验，这种性质的肝细胞聚集体不会发生在Reye综合征或其代谢模拟物中，除了上面列出的缺陷子集。肝活检中这些聚集物的鉴定可能缩小Reye样综合征伴弥漫性肝细胞脂肪变性的鉴别诊断范围。
Metabolic disorders of ureagenesis can cause a Reye-like syndrome with potentially fatal hyperammonemia in children, A mechanistically heterogeneous subset of these disorders shares the biochemical end-result of impaired mitochondrial citrulline production, These include deficiencies of the mitochondrial enzymes, ornithine transcarbamylase (OTC) and carbamyl-phosphate synthase (CPS), as well as dibasic amino-acidurias hyperammonemia-hyperornithinemia-homocitrullinuria (I-II-II-I) and lysinuric protein intolerance (LPI). In this report, we present histopathology of the liver in 10 children with defects of ureagenesis, including 6 with OTC deficiency, 3 with CPS deficiency, and 1 with HHH. The liver showed diffuse microvesicular steatosis, marked periportal nuclear glycogen, and variable portal fibrosis with occasional delicate portal-to-portal bridging, Discrete aggregates of distended hepatocytes with central nuclei and nonvacuolated clear cytoplasm were present in 5 of the 10 children, including two 2 OTC deficiency, 2 with CPS deficiency, and 1 with HHH. Similar aggregates had been previously noted in the liver of some children with OTC deficiency or LPI, but their nature and diagnostic significance had so far remained unknown. Using special stains on frozen tissue sections and electron microscopy, we show that the hepatocytes in these aggregates have little or no cytoplasmic neutral fat, but contain excessive free cytoplasmic glycogen, morphologically mimicking a glycogen storage disease. In our experience, hepatocellular aggregates of this nature do not occur in Reye syndrome or in any of its metabolic mimics other than the subset of defects listed above. Identification of these aggregates on liver biopsy can potentially narrow the differential diagnosis of a Reye-like syndrome with diffuse hepatocellular steatosis.