A recently published case report highlights the vital importance of continued surveillance of antidrug antibody titers in managing patients with Pompe disease receiving enzyme replacement therapy (ERT).

ERT with recombinant human acid α-glucosidase (rhGAA) has significantly improved outcomes and quality of life in patients with PD since its release 17 years ago. However, clinical improvement can be limited by cross-reactive immunologic material (CRIM) development and high sustained antibody titers (HSAT).

The case, published in Molecular Genetics and Metabolism Reports, involved a 15-year-old patient with PD who had received enzyme replacement therapy for 11 years. During this time, the patient maintained low antidrug antibody titers and showed significant clinical improvement in ambulation and endurance. Despite undergoing spinal fusion with rod insertion due to scoliosis at age 12, the patient experienced no significant change in clinical status.

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At 13.8 years of age, the patients developed a significant increase in antidrug antibody titers. Less than a year later, the family reported clinical decline, including worsening gait, balance, and endurance, as well as intermittent diarrhea and bowel urgency after meals.

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In light of clinical and laboratory findings, the patient was started on an immunomodulatory protocol with bortezomib, rituximab, methotrexate, and intravenous immunoglobulin (IVIG). The patients received 2 courses of treatment due to a low response to the first course. Eight weeks after the second course, there was a significant decrease in HSAT.

After the elimination of HSAT, the patient reported significant clinical improvement in gait and endurance, even slightly better than before HSAT.

The patient continued on regular intervals of treatment with rituximab, methotrexate, and IVIG for approximately 3 years without presenting any adverse effects to immunomodulatory therapy.

“Pompe disease patients who develop HSAT can have successful reduction of antidrug IgG titers with immunomodulation therapy and remain on high-dose rhGAA for continued clinical benefit,” the authors concluded.


Kim KH, Desai AK, Vucko ER, Boggs T, Kishnani PS, Burton BK. Development of high sustained anti-drug antibody titers and corresponding clinical decline in a late-onset Pompe disease patient after 11+ years on enzyme replacement therapy.  Mol Genet Metab. Published online June 13, 2023. doi:10.1016/j.ymgmr.2023.100981