Abstract

BackgroundThough enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome.MethodsEight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated.ResultsAll eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3–5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation.ConclusionsOur data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions.

Highlights

  • Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years

  • Motor function was examined using the Alberta Infant Motor Scale (AIMS) (Piper and Darrah 1994) and the achievement of motor milestones was examined at regular clinical assessments

  • We included eight patients with classic infantile Pompe disease, four of whom were treated with alglucosidase alfa in a dose of 20 mg/kg eow and four with 40 mg/kg/week

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Summary

Introduction

Though enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. Patients with the classic infantile form present in the first months of life with generalized muscle weakness, hypertrophic cardiomyopathy, respiratory problems, and feeding difficulties (van den Hout et al 2003). If untreated, they usually die before one year of age due to cardio-respiratory insufficiency. Patients’ prospects were significantly improved in 2006, when enzyme-replacement therapy (ERT) with recombinant human acid α-glucosidase (Myozyme®, alglucosidase alfa) was approved.

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