In Utero Enzyme-replacement Therapy for Infantile-onset Pompe Disease

( N Engl J Med . 2022;387(23):2150–2158. doi: 10.1056/NEJMoa2200587) Early-onset lysosomal storage diseases often involve multiple organ systems, and organ damage begins in utero. In many cases, the damage is severe enough that affected infants do not live long, with the duration of life affected greatly based on what organ systems are affected and how severely. Individuals with these diseases are good candidates for in utero enzyme-replacement therapy (ERT) with recombinant enzymes. Previous studies in animal models have shown that this therapy can mitigate the effect of disease, though not eradicate it. This study was a report of a phase 1 clinical trial that included ERT treatment for an infant diagnosed with Pompe disease, which is caused by acid α-glucosidase (GAA) enzyme deficiency. Without treatment, Pompe disease is typically fatal by 2 years of age and often results in prenatal hypertrophic cardiomyopathy and hypotonia at birth. This article describes the treatment of a cross-reactive immunologic material (CRIM)-negative fetus with infantile-onset Pompe disease after the early postnatal death of 2 older siblings.