Linari Silvia, Castaman Giancarlo
a Department of Heart and Vessels, Center for Bleeding Disorders , Careggi University Hospital , Florence , Italy.
Expert Rev Hematol. 2016 Jan;9(1):51-8. doi: 10.1586/17474086.2016.1112732. Epub 2015 Nov 13.
Gaucher disease is a multisystemic metabolic disorder due to a genetic deficiency of the lysosomal enzyme glucocerebrosidase, which leads to the accumulation within the lysosomes of macrophages of its natural substrate, glucosylceramide and its deacylated product glucosylsphingosine. The most prevalent form of the disease is the so-called non-neuronopathic form (type 1) characterized by anemia, thrombocytopenia, enlargement of liver and/or spleen, skeletal abnormalities. Etiology of anemia and thrombocytopenia may be multifactorial and not necessarily predicted by the degree of splenomegaly. Bleeding diathesis may not always be related to absolute platelet count but may be influenced by abnormal platelet function or coagulation factor deficiencies. A significant increased risk of severe hematological co-morbidities, including multiple myeloma and B-cell lymphoma, has been reported. Accumulation of glucosylceramide and glucosylsphingosyne in macrophages and the resulting chronic inflammation with the secretion of cytokines leading to polyclonal and monoclonal B cell proliferation up to multiple myeloma, as a continuum clonal expansion, is a key pathophysiological mechanism. Enzyme replacement therapy has been shown to be effective in reducing glucosylceramide storage burden and the deleterious effects caused by its accumulation, including hematological manifestations.
戈谢病是一种多系统代谢紊乱疾病，由于溶酶体酶葡萄糖脑苷脂酶的基因缺陷，导致其天然底物葡萄糖神经酰胺及其脱酰基产物葡萄糖神经鞘氨醇在巨噬细胞的溶酶体内蓄积。该疾病最常见的形式是所谓的非神经病变型（1型），其特征为贫血、血小板减少、肝脏和/或脾脏肿大、骨骼异常。贫血和血小板减少的病因可能是多因素的，不一定由脾肿大程度预测。出血倾向不一定总是与血小板绝对计数有关，可能受血小板功能异常或凝血因子缺乏的影响。据报道，严重血液系统合并症（包括多发性骨髓瘤和B细胞淋巴瘤）的风险显著增加。葡萄糖神经酰胺和葡萄糖神经鞘氨醇在巨噬细胞中的蓄积以及由此产生的慢性炎症，伴随着细胞因子的分泌，导致多克隆和单克隆B细胞增殖直至多发性骨髓瘤，作为连续的克隆性扩增，是关键的病理生理机制。已证明酶替代疗法在减轻葡萄糖神经酰胺储存负担及其蓄积所造成的有害影响（包括血液学表现）方面有效。
