Early initiation of enzyme replacement therapy as facilitated by newborn screening improves health outcomes among patients with infantile-onset Pompe disease.

PURPOSE: To assess the benefits of early enzyme replacement therapy (ERT) in patients with infantile-onset Pompe disease (IOPD).

METHODS

A retrospective chart review of 17 IOPD (7 cross-reactive immunologic material [CRIM]-negative and 10 CRIM positive) who initiated ERT (alglucosidase alfa) ≤4 weeks of age and had ≥18 months follow-up was performed.

RESULTS

Patients received starting doses of 20 mg/kg/every other week (n = 11), 20 mg/kg/week (n = 3), or 40 mg/kg/week (n = 3). Six CRIM-negative and 2 patients who were CRIM positive received immune tolerance induction (ITI) with Rituximab+Methotrexate+intravenous immunoglobulin. Five patients who were CRIM positive received transient low-dose methotrexate. All CRIM-negative patients were immune tolerant. Three patients who were CRIM positive developed high-sustained antibody titers (HSAT); 2 were immune tolerant after bortezomib-based ITI. One patient who was CRIM positive developed HSAT, was invasively ventilated, and succumbed at age 5.2 years. At the most recent follow-up (MRFU; 3.1-18.4 years), 16 patients were alive, ambulatory, feeding orally, invasive ventilator-free, and receiving high-dose ERT (median lifelong dose 2.76X; 1.36-4.00). All patients experienced left ventricular mass index and Glc4 reductions and for a subset, biomarkers were within normal limits at MRFU (left ventricular mass index:16/17, AST:9/17, CK:5/17, and Glc4:5/16).

CONCLUSION

These data highlight the benefits of early ERT initiation and ITI, along with high-dose ERT. Despite early treatment, patients with IOPD remain at risk of developing HSAT.