In a first, doctors treat a deadly genetic condition before birth

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A toddler is doing well after doctors in the United States and Canada used a new technique to treat her before she was born for a rare genetic condition that killed two of her sisters.

Ayla Bashir, a 16-month-old child from Ottawa, Ontario, is the first child treated as a fetus for Pompe disease, an inherited and often fatal disease in which the body fails to manufacture some or all of an essential protein.

Today, she is an active and happy girl who has reached the milestones of her development, according to her father, Zahid Bashir, and mother, Sobia Qureshi.

“She’s just an ordinary one-and-a-half-year-old little girl keeping us on our toes,” Bashir said. The couple previously lost two daughters, Zara, 2 1/2, and Sara, 8 months, to illness. A third pregnancy was terminated due to illness.

In a case study published Wednesday in the New England Journal of Medicine, doctors describe an international collaboration during the COVID-19 pandemic that led to the treatment that may have saved Ayla’s life — and expanded the field of potential fetal therapies. Ayla’s outlook is bright but uncertain.

“It is a ray of hope to be able to treat them in utero instead of waiting until the damage is already well established,” said Dr. Karen Fung-Kee-Fung, specialist in maternal-fetal medicine at The Hospital. of Ottawa, who gave the treatment and delivered Ayla.

Fung-Kee-Fung was following a new treatment plan developed by Dr. Tippi MacKenzie, pediatric surgeon and co-director of the Center for Maternal-Fetal Precision Medicine at the University of California, San Francisco, who shared his research after the pandemic prevented the Ayla’s mother to travel for treatment.

“We were all motivated to make this happen for this family,” MacKenzie said.

Doctors treated fetuses before birth for three decades, often with surgery to repair birth defects such as spina bifida. And they gave blood transfusions to the fetuses through the umbilical cord, but no medicine. In this case, the crucial enzymes were delivered through a needle inserted into the mother’s abdomen and guided into a vein in the umbilical cord. Ayla received six infusions every two weeks which began at around 24 weeks 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 been taking care of Ayla’s family for years. “The innovation was to treat earlier and to treat while he was still in utero.”

The unusual partnership also involved experts from Duke University in Durham, North Carolina, which conducted research on Pompe disease, and the University of Washington in Seattle.

Babies with Pompe disease are often treated soon after birth with replacement enzymes to slow the devastating effects of the disease, which affects fewer than 1 in 100,000 newborns. It is caused by mutations in a gene which makes an enzyme that breaks down glycogen, or stored sugar, in cells. When this enzyme is reduced or eliminated, glycogen builds up dangerously throughout the body.

Additionally, the most severely affected babies, including Ayla, suffer from an immune disease in which their bodies block the infused enzymes, which eventually stops the treatment from working. The hope is that treating Ayla early will reduce the severity of this immune response.

Babies with Pompe disease have difficulty feeding, muscle weakness, limpness and often an enlarged heart. Without treatment, most die of heart or respiratory problems within the first year of life.

At the end of 2020, Bashir and Qureshi had learned that they were expecting Ayla and that prenatal tests showed that she too had Pompe disease.

“It was very, very scary,” Qureshi recalled. Apart from the deceased daughters, the couple have a son, Hamza, 13, and a daughter, Maha, 5, who are not affected.

Both parents carry a recessive gene for Pompe disease, which means there is a 1 in 4 chance that a baby will inherit the disease. Bashir said their decision to carry out additional pregnancies was guided by their Muslim faith.

“We believe that what lies ahead is part of what is or is meant for us,” he said. They have no plans for more children, they said.

Chakraborty had heard of MacKenzie’s early trial to test enzyme therapy and thought early treatment might be a solution for the family.

The treatment could be “potentially very important,” said Dr. Brendan Lanpher, a medical geneticist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the research.

“It’s a progressive disease that builds up over time, so every day a fetus or baby gets it, it builds up more material that affects muscle cells.”

Still, it’s too early to tell if the protocol will become an accepted treatment, said Dr. Christina Lam, acting medical director of biochemical genetics at the University of Washington and Seattle Children’s Hospital in Seattle.

“It’s going to take a while to really be able to establish the evidence to definitely show that the results are better,” she said.

Ayla receives drugs to suppress her immune system and weekly enzyme infusions that take five to six hours – a growing challenge for a restless toddler, her mum said. Unless a new treatment emerges, Ayla can expect to continue lifelong infusions. She’s developing normally – for now. Her parents say each milestone, like the moment she started crawling, is especially precious.

“It’s surreal. It amazes us every time,” Qureshi said. “We are so blessed. We have been very, very blessed.

—Jonel Aleccia, Associated Press

Health Sciences

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