Yano Shoji, McGowan Rachel, Warren Mikako
Genetics Division, Pediatrics, Los Angeles General Hospital, University of Southern California, Los Angeles, CA, USA.
Pathology and Laboratory Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA.
Mol Genet Metab Rep. 2024 Jun 14;40:101106. doi: 10.1016/j.ymgmr.2024.101106. eCollection 2024 Sep.
Hearing loss is frequently associated with Gaucher disease (GD). Gaucher cells are enlarged reticuloendothelial cells containing glucocerebroside in the lysosomes due to deficiency of the glucocerebrosidase. Gaucheromas consist of accumulated Gaucher cells. Gaucher cells accumulate in variable tissues including the liver, spleen, bone marrow, and the middle ear and the mastoid causing conductive hearing loss. Neurons and astrocytes in the central nervous system are affected in neuronopathic GD leading to sensorineural hearing loss. Gaucheromas can develop even in patients treated with enzyme replacement therapy (ERT). We report a 19-year-old female patient with GD type 3 who developed profound bilateral hearing loss associated with intracranial Gaucheroma. Combination therapy of ERT with imiglucerase and substrate reduction therapy (SRT) with eliglustat significantly decreased the size of Gaucher cells and cleared the characteristic microtubular structures in the lysosomes in Gaucher cells. Early implementation of SRT may prevent at least conductive hearing impairment in GD although it may not prevent sensorineural hearing loss due to inner hair cell dysfunction which is also known to be associated with neuronopathic GD.
听力损失常与戈谢病（GD）相关。由于葡萄糖脑苷脂酶缺乏，戈谢细胞是溶酶体中含有葡萄糖脑苷脂的肿大网状内皮细胞。戈谢瘤由聚集的戈谢细胞组成。戈谢细胞在包括肝脏、脾脏、骨髓、中耳和乳突在内的多种组织中积聚，导致传导性听力损失。中枢神经系统中的神经元和星形胶质细胞在神经病变型戈谢病中受到影响，导致感音神经性听力损失。即使在接受酶替代疗法（ERT）治疗的患者中也可能出现戈谢瘤。我们报告一名19岁3型戈谢病女性患者，其出现与颅内戈谢瘤相关的双侧严重听力损失。伊米苷酶ERT与依洛尤单抗底物减少疗法（SRT）的联合治疗显著减小了戈谢细胞的大小，并清除了戈谢细胞溶酶体中的特征性微管结构。早期实施SRT可能至少预防戈谢病中的传导性听力损害，尽管它可能无法预防由于内毛细胞功能障碍导致的感音神经性听力损失，内毛细胞功能障碍也已知与神经病变型戈谢病相关。
