Bonesteele Grant, Gargus J Jay, Curtin Emily, Tang Mabel, Rosenbloom Barry, Kimonis Virginia
Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, United States of America.
Department of Physiology, University of California, Irvine, United States of America.
Mol Genet Metab Rep. 2020 Oct 21;25:100663. doi: 10.1016/j.ymgmr.2020.100663. eCollection 2020 Dec.
Gaucher disease type 1 (GD1) is the most common lysosomal storage disease and affects nearly 1 in 40,000 live births. In addition, it is the most common genetic disorder in the Ashkenazi Jewish population with phenotypic variation presenting in early childhood to asymptomatic nonagenarians. There have been a number of studies showing an increased risk of certain malignancies in patients, especially non- Hodgkin's lymphoma (NHL) and multiple myeloma. We describe a 66-year-old Ashkenazi Jewish male with GD1 who was first started on enzyme replacement therapy (ERT) with imiglucerase for GD1 at age 57 years, followed a year later by the diagnosis of diffuse large b-cell non-Hodgkin's lymphoma (DLBCL). He was treated with (cyclophosphamide, doxorubicin, vincristine, and prednisone, plus the monoclonal antibody rituximab), however relapsed and developed myelodysplasia necessitating an allo-stem-cell transplantation but succumbed to severe graft vs. host disease. In addition, we also describe a 38-year-old Ashkenazi Jewish male with GD1 who was diagnosed with DLBCL at age 22 years with Gaucher disease diagnosed on pre-treatment bone marrow biopsy which was confirmed by enzyme assay and genotyping. At age 24 years, he was started on ERT with imiglucerase and at age 35 years, he switched to eliglustat. He has remained in remission from the lymphoma. A meta-analysis of the literature will be elaborated upon and we will discuss the relationship of GD1 to NHL and discuss more recent information regarding lyso-GL1 and the development of NHL and multiple myeloma.
1型戈谢病（GD1）是最常见的溶酶体贮积病，每40000例活产中约有1例受影响。此外，它是阿什肯纳兹犹太人群中最常见的遗传性疾病，表型变异出现在幼儿期至无症状的九旬老人中。有多项研究表明，患者患某些恶性肿瘤的风险增加，尤其是非霍奇金淋巴瘤（NHL）和多发性骨髓瘤。我们描述了一名66岁的阿什肯纳兹犹太男性，患有GD1，他57岁时首次开始用伊米苷酶进行酶替代疗法（ERT）治疗GD1，一年后被诊断为弥漫性大B细胞非霍奇金淋巴瘤（DLBCL）。他接受了（环磷酰胺、阿霉素、长春新碱和泼尼松，加单克隆抗体利妥昔单抗）治疗，但复发并发展为骨髓发育异常，需要进行异基因干细胞移植，但最终死于严重的移植物抗宿主病。此外，我们还描述了一名38岁的阿什肯纳兹犹太男性，患有GD1，他22岁时被诊断为DLBCL，治疗前骨髓活检诊断为戈谢病，酶分析和基因分型证实了这一诊断。24岁时，他开始用伊米苷酶进行ERT治疗，35岁时，他改用艾考糖酯。他的淋巴瘤一直处于缓解状态。将详细阐述对文献的荟萃分析，我们将讨论GD1与NHL的关系，并讨论有关溶血-GL1以及NHL和多发性骨髓瘤发展的最新信息。
