Background

Pompe disease (PD) is a lysosomal glycogen storage disorder caused by a deficiency in acid α-glucosidase (GAA) activity. Various organs, including the skeletal muscle, cardiac muscle, and liver, are commonly involved. Early initiation of enzyme replacement therapy (ERT) with recombinant human α-glucosidase (rhGAA) can improve the outcome. However, some patients experience a poor clinical course despite ERT because of the emergence of anti-rhGAA antibodies that neutralize rhGAA. Treatment against anti-rhGAA antibodies is challenging.

Case–diagnosis/treatment

A 14-year-old boy with late-onset PD was referred to our hospital with proteinuria detected by school urinalysis screening. He was diagnosed with PD at the age of 4 years based on muscle biopsy and decreased GAA activity. Treatment with rhGAA was initiated, but anaphylaxis occurred frequently. Anti-rhGAA antibodies were detected and immune tolerance therapy was therefore given, but his antibody titer remained high. Kidney biopsy revealed stage II membranous nephropathy. Immunohistochemistry staining revealed anti-rhGAA antibody/rhGAA immune complexes along the glomerular capillary loop. Aggressive immunotherapy combined with bortezomib and rituximab was then initiated. Serum levels of anti-rhGAA antibodies decreased significantly and his proteinuria finally resolved.

Conclusions

There have been few reports of membranous nephropathy associated with ERT for PD. We clarified the cause in the current patient. Bortezomib and rituximab effectively suppressed anti-rhGAA antibody production resulting in the resolution of proteinuria and maintenance of ERT efficacy.

中文翻译：

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积极的免疫疗法联合硼替佐米和利妥昔单抗治疗庞贝病酶替代疗法相关的膜性肾病

背景

庞贝病 (PD) 是由酸性 α-葡萄糖苷酶 (GAA) 活性缺陷引起的溶酶体糖原贮积症。通常涉及各种器官，包括骨骼肌、心肌和肝脏。早期开始使用重组人 α-葡萄糖苷酶 (rhGAA) 进行酶替代疗法 (ERT) 可以改善结果。然而，由于中和 rhGAA 的抗 rhGAA 抗体的出现，尽管进行了 ERT，一些患者的临床过程仍然很差。针对抗 rhGAA 抗体的治疗具有挑战性。

病例诊断/治疗

一名患有迟发性 PD 的 14 岁男孩被转诊到我们医院，通过学校尿液分析筛查检测到蛋白尿。根据肌肉活检和 GAA 活性降低，他在 4 岁时被诊断出患有 PD。开始用 rhGAA 治疗，但经常发生过敏反应。检测到抗rhGAA抗体，给予免疫耐受治疗，但抗体滴度仍然很高。肾活检显示 II 期膜性肾病。免疫组织化学染色揭示了沿肾小球毛细血管环的抗 rhGAA 抗体/rhGAA 免疫复合物。然后开始联合硼替佐米和利妥昔单抗的积极免疫治疗。抗 rhGAA 抗体的血清水平显着下降，他的蛋白尿终于消失了。

结论

很少有关于 PD 的 ERT 相关的膜性肾病的报道。我们澄清了当前患者的病因。硼替佐米和利妥昔单抗有效地抑制了抗 rhGAA 抗体的产生，从而解决了蛋白尿并维持了 ERT 功效。