In a 1st, child treated for rare, often-fatal disorder while still in the womb

In a first, doctors began treating a child's rare genetic disorder before she was born. The child, who is now 16 months old, will still require treatment for the rest of her life, but starting her therapy early meant she was born without overt signs of the disorder and with the chance of a better prognosis.

The unique case was described in a report published Wednesday (Nov. 9) in The New England Journal of Medicine.

The child, Ayla Bashir, was born in Ottawa, Ontario, and her parents, Sobia Qureshi and Zahid Bashir, said she's happy and meeting her developmental milestones. "She's just a regular little 1½-year-old who keeps us on our toes," Zahid Bashir, her father, told The Associated Press (AP).

Due to a recessive gene variant that both Qureshi and Bashir carry, their children have a 25% chance of inheriting Pompe disease, an often fatal disorder that affects fewer than 1 in 100,000 live births, according to a statement from the University of California, San Francisco. The couple previously lost two children to the disorder, both in infancy.

Related: New gene-therapy gel shows promise for treating rare 'butterfly disease'

Pompe disease is caused by mutations in the gene that codes for acid alpha-glucosidase (GAA), an enzyme the body needs to break down glycogen, or stored sugar, into usable fuel for cells. The disorder limits or eliminates GAA in the body, causing glycogen to rapidly accumulate and damage tissues, especially muscles. 

Some people with a less-severe form of Pompe disease develop symptoms later in life, according to the National Institute of Neurological Disorders and Stroke, but Ayla has infantile-onset Pompe disease, which typically starts in the womb. Ayla was diagnosed during a prenatal screening for chromosomal and other genetic abnormalities. 

Before treatments for Pompe disease became available, most babies with infantile-onset Pompe disease died of cardiac or respiratory complications before their first birthdays, Dr. Ans van der Ploeg, chair of the Center for Lysosomal and Metabolic Diseases at the Erasmus MC University in Rotterdam, Netherlands, wrote in a commentary. (Van der Ploeg was not involved in Ayla's care.) 

Now, affected babies can receive regular infusions of the GAA enzyme after birth; the first infants who received this therapy are now in their 20s, van der Ploeg wrote. However, the treatment doesn't prevent the organ damage that unfolds in the womb, and even when treated, Pompe disease can result in poor muscle tone, respiratory problems and death.

So Dr. Tippi MacKenzie, a fetal and pediatric surgeon at UCSF Benioff Children's Hospitals, launched a clinical trial in which doctors will start treating Pompe disease and similar disorders before birth, in order to prevent serious organ damage.

Qureshi was referred for this trial in 2020 but couldn't travel to UCSF due to the pandemic. Instead, MacKenzie and her collaborators at Duke University worked with two institutions in Canada — The Ottawa Hospital and the Children's Hospital of Eastern Ontario (CHEO) — to coordinate treatment from afar. 

Starting around week 24 of her pregnancy, Qureshi received biweekly infusions of the GAA enzyme into a vein in the umbilical cord. She received a total of six prenatal infusions at The Ottawa Hospital, and since birth, Ayla has gotten weekly infusions at CHEO, the AP reported.

Ayla was born without thickened heart muscles or general muscle weakness, both of which are common symptoms of Pompe disease, and was still free of these symptoms at the time the report was written, according to van der Ploeg. "Further follow-up of this patient will be important," but so far, the course of her development has been "encouraging," he wrote.