Gilbert-Barness E, Barness L A, Meisner L F
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706.
Pediatr Pathol. 1990;10(1-2):243-52. doi: 10.3109/15513819009067111.
Autopsy of a 4-year-old girl with hereditary tyrosinemia type I revealed a hepatocellular carcinoma in addition to cirrhosis and renal tubular dysplasia. Cytogenetic studies performed on a skin fibroblast culture demonstrated greatly increased chromosome breakage, which affected 71% of the cells. This suggests that the development of hepatoma, which is frequent in this syndrome, and the presence of dysplastic changes of hepatocytes in nontumorous liver are related to genetic instability caused by accumulation of intermediates of tyrosine catabolism, which are natural alkylating agents (e.g., maleylacetoacetate and fumarylacetoacetate). The other microscopic structural changes seen, such as renal tubular atypia, pancreatic islet cell hyperplasia, and focal necrosis of cortical neurons, may also be partly due to DNA damage caused by the accumulation of abnormal metabolites produced in patients with type 1 tyrosinemia.
对一名患有I型遗传性酪氨酸血症的4岁女孩进行尸检发现，除了肝硬化和肾小管发育异常外，还存在肝细胞癌。对皮肤成纤维细胞培养物进行的细胞遗传学研究表明，染色体断裂显著增加，71%的细胞受到影响。这表明，该综合征中常见的肝癌发生以及非肿瘤性肝脏中肝细胞发育异常变化的存在，与酪氨酸分解代谢中间产物的积累导致的基因不稳定有关，这些中间产物是天然烷基化剂（如马来酰乙酰乙酸和富马酰乙酰乙酸）。所观察到的其他微观结构变化，如肾小管异型性、胰岛细胞增生和皮质神经元局灶性坏死，也可能部分归因于1型酪氨酸血症患者体内异常代谢产物积累所导致的DNA损伤。
