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In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe’s Disease

In a case report of a fetus with CRIM (cross-reactive immunologic material)–negative infantile-onset Pompe’s disease, in utero enzyme-replacement therapy (ERT) was safe and effective. “Direct umbilical-vein administration of therapeutic compounds can be accomplished safely by physicians experienced with in utero blood transfusions,” the investigators conclude. “Like any fetal intervention, this procedure carries a risk of preterm delivery. Nondirective counseling for parents of affected pregnancies is critical to ensure informed choices regarding the risk–benefit profile of this new therapy. Our phase 1 clinical trial of in utero ERT for fetuses with genetically confirmed early-onset lysosomal storage diseases will enable the collection of additional safety and efficacy data in a larger cohort.”

In this case, the family history was positive for infantile-onset Pompe’s disease with cardiomyopathy in 2 previously affected deceased siblings. Alglucosidase alfa 20 mg per kilogram of estimated fetal weight was administered under ultrasonic guidance through the umbilical vein beginning at 24 weeks 5 days of gestation and continued at 2-week intervals through 34 weeks 5 days of gestation (6 infusions total). Standard postnatal therapy included alglucosidase alfa 20 mg/kg/dose on day 4 and then every other week (with higher and more frequent doses during the latter part of the first year of life), testing for acid α-glucosidase enzyme activity, and serum antidrug antibody titers. The patient “had normal cardiac and age-appropriate motor function postnatally, was meeting developmental milestones, had normal biomarker levels, and was feeding and growing well at 13 months of age,” the authors report.

Source: New England Journal of Medicine