Management of life-threatening anaphylaxis to enzyme replacement therapy in an infant with Pompe disease: a case report and literature review

Background Infantile-onset Pompe disease (IOPD) is a life-threatening lysosomal storage disorder, caused by deficiency of the acid alpha-glucosidase (GAA) enzyme. While enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) is the standard treatment, its efficacy in cross-reactive immunological material (CRIM)-negative patients is often complicated by severe infusion-associated reactions (IARs), posing significant challenges to management. Methods We present a case of a CRIM-negative IOPD patient carrying a novel homozygous nonsense mutation in the GAA gene (c.2237G > A, p.Trp746*). Diagnosis was confirmed by significantly reduced GAA enzyme activity and genetic analysis. The patient was started on ERT using a desensitization protocol. Results Despite initial desensitization, the patient experienced recurrent IARs, which progressed to life-threatening anaphylaxis (Grade 5, according to the WAO grading system for allergic reactions). Conventional preventive strategies including corticosteroid premedication, reduction of infusion rate, and dose reduction, failed to prevent the recurrences of severe reactions. A novel approach involving continuous epinephrine co-infusion with low-concentration rhGAA (1 mg/mL) was subsequently implemented, which may represent a potential rescue strategy to prevent further IARs and allow for continued ERT. Unfortunately, the patient ultimately died from severe pulmonary infection at 15 months of age. Conclusion For CRIM-negative IOPD patients who develop refractory anaphylaxis to ERT, continuous epinephrine co-infusion represents a viable rescue strategy to facilitate treatment. This case underscores the critical need for early immune tolerance induction and the development of novel therapeutic modalities for this high-risk population.