Gragnaniello and colleagues address the best current management for enzyme replacement therapy (ERT) adverse reactions in patients with infantile-onset Pompe disease (IOPD) and published their results in the Italian Journal of Pediatrics.

IOPD without treatment can cause death within the first 2 years of life, and alglucosidase alfa is currently the only treatment available as part of ERT. The dosage of alglucosidase alfa varies from 20 mg/kg to 40 mg/kg, yielding the latter for more satisfactory outcomes. ERT improves motor functions, cardiomyopathy, and ventilator-free plus overall survival, however, it has severe adverse reactions.

“Two types of immune reactions against ERT have been reported: 1) infusion associated reactions (IARs) including hypersensitivity responses with or without increase of specific immunoglobulin E (IgE) and 2) development of specific immunoglobulin G (IgG) which reduces treatment efficacy,” the authors said.

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Nearly 50% of patients with IOPD show infusion-associated reactions, involving a wide array of cutaneous, cardiac, respiratory, or gastrointestinal systems. From that percentage, 5% to 14% have at least 2 body systems involved, and 1% develop anaphylactic shock and/or cardiac arrest, requiring life support measures.

On the other hand, nearly 90% of the patients with IOPD develop IgG who are treated with alglucosidase alfa. Patients with IOPD were even classified according to their IgG anti-alglucosidase alfa titers as high and sustained, sustained intermediate, and low titers.

The high and sustained antibody titers group were linked to clinical worsening, and the sustained intermediate group also showed reduced enzyme efficacy. “It appears that the persistence of sustained titers for a long period of time, rather than the absolute values of the titers, impairs the ERT efficacy and thus the clinical outcome,” the authors said.

The researchers developed treatment algorithms to explain how to screen and/or prevent possible adverse effects or decrease the effectiveness of ERT, and concluded that new antigen-specific and/or more highly antigen-targeted protocols can improve safety and efficacy. They also recommend more personalized treatment approaches such as immunogenicity prediction prior to initiating ERT, especially in patients who are positive for cross-reactive immunological material.


Gragnaniello V, Deodato F, Gasperini S, et al. Immune responses to alglucosidase in infantile Pompe disease: recommendations from an Italian pediatric expert panelItal J Pediatr. 2022;48(1). doi:10.1186/s13052-022-01219-4