Royal Free London NHS Foundation Trust, London, UK.
SphinCS Hocheim, Germany.
Mol Genet Metab. 2021 Aug;133(4):335-344. doi: 10.1016/j.ymgme.2021.06.009. Epub 2021 Jun 25.
Gaucher disease (GD) is a rare lysosomal storage disorder classically subdivided into type 1 (non-neuronopathic) GD, and types 2 and 3 (neuronopathic) GD. It is typically characterized by clinical manifestations including anemia, thrombocytopenia, hepatosplenomegaly, bone lesions, and (in more severe forms) neurological impairment. However, less-commonly reported and often under-recognized manifestations exist, which potentially have a significant impact on patient outcomes. Greater efforts are needed to understand, recognize, and manage these manifestations.
This review provides a synthesis of published information about three under-recognized GD manifestations (pulmonary involvement, lymphadenopathy, and Gaucheroma) and recommends diagnostic, management, and treatment strategies based on the available literature and author experience. The authors aim to raise awareness about these serious, progressive, and sometimes life-threatening conditions, which are often diagnosed late in life.
Little is known about the incidence, pathophysiology, prognostic factors, and optimal management of pulmonary involvement, lymphadenopathy, and Gaucheroma in patients with GD. Enzyme replacement therapy (ERT) has shown limited efficacy for the prevention and treatment of these manifestations. More research is needed to evaluate the potential effect of substrate reduction therapy (SRT) with glucosylceramide synthase (GCS) inhibitors, and to develop additional approaches to treat these GD manifestations. Improvements in data collection registries and international data-sharing are required to better understand the impact of these manifestations on GD patients, help develop effective management strategies, and, ultimately, improve patient outcomes.
戈谢病（Gaucher disease，GD）是一种罕见的溶酶体贮积病，经典地分为 1 型（非神经病变型）GD、2 型和 3 型（神经病变型）GD。其典型特征包括临床表现，如贫血、血小板减少、肝脾肿大、骨骼病变和（在更严重的形式中）神经功能损伤。然而，也存在一些较少报道且常被低估的表现，这些表现可能对患者结局有重大影响。需要做出更大努力来理解、识别和管理这些表现。
本综述汇总了已发表的关于三种被低估的 GD 表现（肺部受累、淋巴结病和 Gaucher 瘤）的信息，并根据现有文献和作者经验推荐了诊断、管理和治疗策略。作者旨在提高对这些严重、进行性且有时危及生命的疾病的认识，这些疾病往往在生命后期才被诊断。
关于 GD 患者肺部受累、淋巴结病和 Gaucher 瘤的发病率、病理生理学、预后因素和最佳管理，人们知之甚少。酶替代疗法（enzyme replacement therapy，ERT）在预防和治疗这些表现方面疗效有限。需要更多的研究来评估葡萄糖脑苷脂合成酶（glucosylceramide synthase，GCS）抑制剂的底物减少疗法（substrate reduction therapy，SRT）的潜在效果，并开发治疗这些 GD 表现的其他方法。需要改进数据收集登记处和国际数据共享，以更好地了解这些表现对 GD 患者的影响，帮助制定有效的管理策略，并最终改善患者结局。
