Khan, Aleena ACase, Laura EHerbert, MruduDeArmey, StephanieJones, HarrisonCrisp, KellyZimmerman, KaneciaElMallah, Mai KYoung, Sarah PKishnani, Priya S2023-05-022023-05-022020-051098-36001530-0366https://hdl.handle.net/10161/27300<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.HumansGlycogen Storage Disease Type IIalpha-GlucosidasesRetrospective StudiesChildChild, PreschoolEnzyme Replacement TherapyJournal article2023-05-02