Kim Min Jin, Suh Jin-Tae, Lee Hee Joo, Lee Woo-In, Moon Ahrim, Lee Juhie, Kang Seong-Ho, Cho Eun Hae, Oh Seung Hwan, Baek Sun Kyung, Kim Si Young, Park Tae Sung
Department of Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Ann Clin Lab Sci. 2012 Summer;42(3):293-301.
Gaucher's disease (GD) is a rare autosomal recessive (AR) disorder characterized by a deficiency of glucocerebrosidase (glucosylceramidase, acid β-glucosidase). This enzyme deficiency results in an accumulation of sphingolipids in the cells of GD patients, which may contribute to the dysregulation of the immune system, B-cell dysfunction and expression of specific cytokines such as interleukin (IL) -1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF). Accumulated substrate may directly affect the patient's immunity and pose a higher risk for cancer, especially hematologic malignancies. However, recent large-scale studies suggest that the relative risks of GD and hematologic malignancies are not statistically significant and, therefore, their association with each other remains controversial. In this report, we present the first Asian GD case where the patient was simultaneously diagnosed with a non-Hodgkin's lymphoma. A renal biopsy confirmed that the patient had diffuse large B-cell lymphoma (DLBCL). A bone marrow study during lymphoma staging revealed Gaucher cells with abundant fibrillary, blue-gray cytoplasm and a wrinkled, tissue paper-like appearance. Subsequently, an acid β-glucosidase (GbA) gene mutation study demonstrating two heterozygote mutations, G202R (c.721G>A; p.G241R), a known pathogenic mutation, and a novel mutation R277C (c.946C>T; p.R316C) prompted the diagnosis of GD. Previous case reports have demonstrated concurrent GD and lymphoma in type 1 GD patients, with 40% of patients diagnosed with GD when a lymphoma is detected during disease evaluation. In Korea, GD cases with the G202R gene mutation have been reported in neuropathic patients with a very low frequency. To our knowledge, this case represents the first observation of the G202R mutation in a type 1 GD patient associated with lymphoma. Furthermore, this report is the first patient with DLBCL with kidney involvement along with GD.
戈谢病（GD）是一种罕见的常染色体隐性（AR）疾病，其特征是葡糖脑苷脂酶（葡萄糖神经酰胺酶，酸性β-葡萄糖苷酶）缺乏。这种酶缺乏导致戈谢病患者细胞中鞘脂积累，这可能导致免疫系统失调、B细胞功能障碍以及特定细胞因子如白细胞介素（IL）-1、IL-6、IL-8、IL-10和肿瘤坏死因子（TNF）的表达。积累的底物可能直接影响患者的免疫力，并增加患癌症的风险，尤其是血液系统恶性肿瘤。然而，最近的大规模研究表明，戈谢病与血液系统恶性肿瘤的相对风险在统计学上并不显著，因此，它们之间的关联仍存在争议。在本报告中，我们介绍了首例同时被诊断为非霍奇金淋巴瘤的亚洲戈谢病患者。肾脏活检证实该患者患有弥漫性大B细胞淋巴瘤（DLBCL）。淋巴瘤分期期间的骨髓检查发现了戈谢细胞，其细胞质丰富、呈纤维状、蓝灰色，外观呈皱缩的薄纸样。随后，一项酸性β-葡萄糖苷酶（GbA）基因突变研究显示了两个杂合子突变，即已知的致病突变G202R（c.721G>A；p.G241R）和新突变R277C（c.946C>T；p.R316C），从而确诊为戈谢病。先前的病例报告显示1型戈谢病患者同时患有戈谢病和淋巴瘤，40%的患者在疾病评估期间检测到淋巴瘤时被诊断为戈谢病。在韩国，G202R基因突变的戈谢病病例在神经性患者中报告的频率非常低。据我们所知，该病例是1型戈谢病患者中首次观察到与淋巴瘤相关的G202R突变。此外，本报告是首例伴有肾脏受累的弥漫性大B细胞淋巴瘤合并戈谢病的患者。
