In utero enzyme replacement therapy (ERT) may lead to appropriate motor function after birth and the achievement of developmental milestones after 13 months of age in patients with Pompe disease (PD), according to a recently published case report in the New England Journal of Medicine

Infantile-onset PD is associated with prenatal cardiopathy and hypotonia at birth. Most untreated patients with the disease do not surpass 2 years of age. 

Although the current availability of newborn screening allows early treatment initiation, this strategy does not fully prevent long-term organ damage and residual myopathy. 

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Therefore, there is high interest in the development of in utero ERTs with the capacity to prevent irreparable organ damage in newborn patients with PD. In utero ERTs have already had promising results in murine models. The authors received approval for a phase 1 clinical trial for in utero therapy for lysosomal storage diseases in which ERT is available.

“We treated a fetus with [cross-reactive immunologic material (CRIM)-negative] infantile-onset Pompe’s disease in the context of the early postnatal demise of 2 previous siblings,” the authors said.

The case involved a 37-year-old pregnant woman with a medical history remarkable for previous pregnancies affected with CRIM-negative infantile onset PD. PD was also diagnosed in the current pregnancy through chorionic villus sampling.

In utero, ERT consisted of the umbilical administration of alglucosidase alfa from 24 weeks, 5 days of gestation, until week 34 in intervals of 2 weeks. After birth, the child received protocol standard-of-care treatment for infantile-onset PD. 

Notably, no adverse reactions occurred, and the patient was delivered vaginally at 37 weeks, 4 days of gestation. Creatinine kinase levels, commonly used as a diagnostic biomarker for PD, remained normal from day 4 after birth until the current assessment at 13 months of age. Furthermore, the patient did not present with motor deficits at birth and achieved all developmental milestones during the follow-up period.

Regarding cardiac function, all echocardiograms performed during the follow-up period were normal, and electrocardiograms were also normal.

Due to the detection of antidrug antibodies, treatment with rituximab was started as a precaution. However, due to persistent low antibody titers, the dose was progressively decreased.

“Although it is accepted that starting treatment as early as possible improves outcomes in patients with lysosomal storage diseases (e.g., when the diagnosis is established after newborn screening), our results suggest that moving the window for therapeutic intervention into the prenatal period may further improve postnatal outcomes,” the authors concluded.


Cohen J, Chakraborty P, Fung-Kee K, et al. In utero enzyme-replacement therapy for infantile-onset Pompe’s disease. N Engl J Med. Published online November 9, 2022. doi:10.1056/nejmoa2200587