Aries Charlotte, Lohmöller Benjamin, Tiede Stephan, Täuber Karolin, Hartmann Guido, Rudolph Cornelia, Muschol Nicole
Department of Pediatrics, International Center for Lysosomal Disorders, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
University Children's Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Neurol. 2022 Jun 6;13:907317. doi: 10.3389/fneur.2022.907317. eCollection 2022.
Gaucher Disease (GD) 2 is a rare inherited lysosomal disorder. Early-onset and rapid progression of neurovisceral symptoms lead to fatal outcome in early childhood. Treatment is symptomatic, a curative therapy is currently not available. This prospective study describes the clinical and biochemical outcome of a GD 2 patient treated with high dose ambroxol from the age of 4 months. Due to progressive hepatosplenomegaly additional enzyme replacement therapy was required 1 year after ambroxol monotherapy was initiated. Detailed clinical follow-up data demonstrated an age-appropriate neurocognitive and motor development but no clear benefit on peripheral organs. Glucosylsphingosine (Lyso-GL1) in cerebrospinal fluid decreased remarkably compared to pre-treatment, whereas Lyso-GL1 and chitotriosidase in blood increased. Ambroxol treatment of patient fibroblasts revealed a significant increase in β-glucocerebrosidase activity . To our knowledge, this is the first report of a GD 2 patient with age-appropriate cognitive and motor development at 3 years of age. Combination of high dose ambroxol with ERT proved to be a successful approach to manage both visceral and neurological manifestations.
戈谢病2型（GD2）是一种罕见的遗传性溶酶体疾病。神经内脏症状的早发和快速进展会导致幼儿期出现致命后果。治疗仅为对症治疗，目前尚无治愈疗法。这项前瞻性研究描述了一名从4个月大开始接受高剂量氨溴索治疗的GD2患者的临床和生化结果。由于进行性肝脾肿大，在开始氨溴索单药治疗1年后需要额外的酶替代疗法。详细的临床随访数据显示神经认知和运动发育符合年龄，但对外周器官没有明显益处。与治疗前相比，脑脊液中的葡萄糖神经酰胺（Lyso-GL1）显著降低，而血液中的Lyso-GL1和壳三糖苷酶增加。氨溴索对患者成纤维细胞的治疗显示β-葡萄糖脑苷脂酶活性显著增加。据我们所知，这是第一例3岁时神经认知和运动发育符合年龄的GD2患者的报告。高剂量氨溴索与酶替代疗法相结合被证明是管理内脏和神经表现的成功方法。
