In a first, doctors treat fatal genetic disease before birth
A toddler is thriving after doctors in the U.S. and Canada used a novel technique to treat her before she was born for a rare genetic disease that caused the deaths of two of her sisters.
Ayla Bashir, a 16-monthold from Ottawa, Ontario, is the first child treated as a fetus for Pompe disease, an inherited and often fatal disorder in which the body fails to make some or all of a crucial protein.
Today, she’s an active, happy girl who has met her developmental milestones, according to her father, Zahid Bashir and mother, Sobia Qureshi.
“She’s just a regular little 1½-year-old who keeps us on our toes,” Bashir said. The couple previously lost two daughters, Zara, 2½, and Sara, 8 months, to the disease.
In a case study published recently in the New England Journal of Medicine, doctors describe an international collaboration during the COVID19 pandemic that led to the treatment that may have saved Ayla’s life — and expanded the field of potential fetal therapies. The outlook for Ayla is promising but uncertain.
“It holds a glimmer of hope for being able to treat them in utero instead of waiting until damage is already well-established,” said Dr. Karen Fung-KeeFung, a maternal-fetal medicine specialist at
The Ottawa Hospital who treated and delivered Ayla.
Fung-Kee-Fung was following a new treatment plan developed by Dr. Tippi MacKenzie, a pediatric surgeon and co-director of the Center for Maternal-Fetal Precision Medicine at the University of California, San Francisco, who
shared her research after the pandemic kept Ayla’s mother from traveling for care.
Doctors have treated fetuses before birth for three decades, often with surgeries to repair birth defects such as spina bifida. And they’ve given blood transfusions to fetuses through the umbilical cord, but not medicines. In this case, the crucial enzymes were delivered through a needle inserted through the mother’s abdomen and guided into a vein in the umbilical cord. Ayla received six biweekly infusions that started at 24 weeks of gestation.
“The innovation here wasn’t the drug and it wasn’t accessing the fetal circulation,” said Dr. Pranesh Chakraborty, a metabolic geneticist at Children’s Hospital of Eastern Ontario, who has cared for Ayla’s family for years. “The innovation was treating earlier and treating while still in utero.”
Babies with Pompe disease are often treated soon after birth with replacement enzymes to slow devastating effects of the condition, which
affects fewer than 1 in 100,000 newborns. It is caused by mutations in a gene that make an enzyme that breaks down glycogen, or stored sugar, in cells. When that enzyme is reduced or eliminated, glycogen builds up dangerously throughout the body.
The most severely affected babies, including Ayla, have an immune condition in which their bodies block the infused enzymes, eventually stopping the therapy from working. The hope is that Ayla’s early treatment will reduce the severity of that immune response.
In late 2020, Bashir and Qureshi had learned they were expecting Ayla and that prenatal tests showed she had Pompe disease.
Both parents carry a recessive gene for Pompe disease, which means there’s a 1 in 4 chance that a baby will inherit the condition. Bashir said their decision to proceed with additional pregnancies was guided by their Muslim faith.
“We believe that what will come our way is part of what’s meant or destined for us,” he said.