Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process
Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process
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DOI：
10.1007/s10545-009-1178-9
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发表时间：
2009-08-01
影响因子：
4.2
通讯作者：
Elleder, M.
中科院分区：
文献类型：
--
作者：
Hulkova, H.;Ledvinova, J.;Elleder, M.
我们报告了一名女性戈谢病（GD） I型患者，接受ERT （imiglucerase）治疗5年，总体情况明显改善。59岁时，她经历了一次高原反应，随后出现败血症、弥散性血管内凝血和多器官衰竭。她死于脑溢血。尸检显示肝脏胆汁淤积性肝硬化和多灶性肝癌，免疫表型与胆管癌相容。对储存过程的分析显示，在大多数肝脏和脾脏巨噬细胞中缺乏或含量极低。戈谢细胞（GCs）在这些器官中仅偶见不同大小的聚集体。在小脑的轻脑膜中也可见GCs，在灰质和白质中也可见少见的血管周围簇状细胞。骨髓大量浸润GCs，尤其是富含脂肪细胞的部分。这个位置的GCs显示不同程度的细胞质空泡化，与溶酶体室无关，由甘油三酯液滴引起，并被解释为由于改变的白色脂肪细胞碎片的吸收。所有这些观察结果都表明ERT在覆盖标准底物负荷方面的相对功效，不应超过这一功效，因为这将导致成熟gc的进化。这些结果与我们最近发表的关于GD细胞病理学的假设有关。
We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickness followed by sepsis, disseminated intravascular coagulation, and multiorgan failure. She succumbed to a cerebral haemorrhage. Autopsy revealed liver cholestatic cirrhosis and multifocal liver carcinoma with immunophenotype compatible with cholangiocarcinoma. Analysis of the storage process revealed its absence or very low levels in the majority of liver and spleen macrophages. Gaucher cells (GCs) were seen only as occasional aggregates of various sizes in these organs. GCs were seen also in the leptomeninx of the cerebellum and as infrequent perivascular clusters in both the grey and white cerebral matters. Bone marrow was heavily infiltrated with GCs, especially in the adipocyte-rich part. GCs in this location displayed varied degrees of cytoplasmic vacuolation unrelated to the lysosomal compartment, caused by droplets of triglyceride, and interpreted as due to resorption of fragments of altered white adipocytes. All these observations point to the relative efficacy of ERT in covering the standard substrate load, which should not be exceeded as it would lead to the evolution of mature GCs. The results are discussed in relation to our recently published hypothesis on GD cell pathology.