For First Time, a Fatal Enzyme Deficiency is Treated in the Womb to Save a Child

An unborn baby was treated through her umbilical cord for a rare genetic condition—the same disease that killed her two older siblings—and the pioneering procedure prevented the infant’s death.

It’s the first time in history Pompe disease has been treated in utero, and it could represent a life-saving new standard of care that’s safe and effective for both mother and infant.

In Canada, the parents of 16-month-old Ayla were relieved when she was born as expected, with no signs of the disease that can cause lethal heart complications. Pompe affects fewer than 1 in 100,000 infants, but this inherited condition arising from a defective gene copy is often fatal.

Treatment so far starts after birth, is known as enzyme replacement therapy (ERT), and plays the role of injecting an enzyme critical for healthy heart function. Pompe disease is known as a “lysosomal storage disorder” and results in the buildup of toxins in tissues. The replacement enzyme is called GAA, and since fetuses and infants like Ayla can’t produce it, toxic buildups of glycogen, the storage form of sugars like glucose, can damage the heart and lead to myocarditis.

The glycogen makes it harder for their small hearts to pump blood, leading to muscle weakness, and death is typical within 2 years.

In March of 2021, Ayla’s mother entered an Ottawa maternal hospital and over the following weeks received 6 injections of an infant-Pompe drug called alglucosidase alfa into the umbilical vein, a delivery method that’s established for treating anemia in a fetus.

Ayla was born on schedule without any signs of the disease. She’s met normal developmental milestones and doesn’t show any loss of motor function. She still receives regular ERT. The results were compiled and published in the New England Journal of Medicine.

“Our results are consistent with in utero ERT attenuating or even halting the disease process in the fetal period,” the doctors wrote in their case report.

“Furthermore, although it is accepted that starting treatment as early as possible improves outcomes in patients with lysosomal storage diseases … our results suggest that moving the window for therapeutic intervention into the prenatal period may further improve postnatal outcomes.”