Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

PURPOSE: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease. METHODS: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained. We obtained physical therapy, lingual strength, biochemical, and pulmonary assessments as dose was escalated. RESULTS: Eleven patients with IPD (n = 7) or LOPD (n = 4) were treated with higher doses of up to 40 mg/kg weekly. There were improvements in gross motor function measure in 9/10 patients, in lingual strength in 6/6 patients, and in pulmonary function in 4/11. Significant reductions in urinary glucose tetrasaccharide, creatine kinase, aspartate aminotransferase, and alanine aminotransferase were observed at 40 mg/kg weekly compared with lower doses (p < 0.05). No safety or immunogenicity concerns were observed at higher doses. CONCLUSION: Higher rhGAA doses are safe, improve gross motor outcomes, lingual strength, pulmonary function measures, and biochemical markers in early-onset Pompe disease, and should be considered in patients with clinical and functional decline.

Duke Scholars

Author Laura Elizabeth Case Orthopaedic Surgery, Physical Therapy

Author Kanecia Obie Zimmerman Pediatrics, Critical Care Medicine

Author Mai ElMallah Pediatrics, Pulmonary and Sleep Medicine

Author Sarah Phyllis Young Pediatrics, Medical Genetics

Author Priya Sunil Kishnani Pediatrics, Medical Genetics