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Aggressive immunotherapy combined with bortezomib and rituximab for membranous nephropathy associated with enzyme replacement therapy in Pompe disease

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Abstract

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.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

We are grateful to Dr. Koji Muroya, Department of Endocrinology and Metabolism, Kanagawa Children’s Medical Center, for his medical advice, and to Professor Kenichi Ohashi, Jikei University School of Medicine, for providing the anti-rhGAA antibody. We thank Melissa Crawford, PhD, and Susan Furness, PhD, from Edanz (https://jp.edanz.com/ac) for editing drafts of this manuscript.

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Authors and Affiliations

  1. Department of Pediatrics, Yokohama City University Medical Center, Yokohama, Japan

    Keigo Sasaki, Toru Uchimura, Aya Inaba & Shuichi Ito

  2. Division of Diagnostic Pathology, Yokohama City University Medical Center, Yokohama, Japan

    Masako Otani

  3. Department of Endocrinology and Metabolism, Kanagawa Children’s Medical Center, Yokohama, Japan

    Junko Hanakawa

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  1. Keigo Sasaki
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  2. Toru Uchimura
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Correspondence to Shuichi Ito.

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Sasaki, K., Uchimura, T., Inaba, A. et al. Aggressive immunotherapy combined with bortezomib and rituximab for membranous nephropathy associated with enzyme replacement therapy in Pompe disease. Pediatr Nephrol 38, 921–925 (2023). https://doi.org/10.1007/s00467-022-05672-5

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  • DOI: https://doi.org/10.1007/s00467-022-05672-5

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