A rare genetic condition has made a girl’s life easier. This was the first time that she had received treatment for this condition.
Sixteen-month-old Ayla has infantile-onset Pompe disease — a genetic disorder that can cause organ damage that begins before birth. Pompe-born babies have larger hearts and weaker muscles. Most infants will die before their second birthday if they are not treated. Treatment typically begins after birth, but that tactic doesn’t prevent the irreversible, and potentially deadly, organ damage that happens in utero.
As part of an early stage clinical trial, Ayla was treated while she was still in her womb. The toddler today has a normal heart rate and is reaching developmental milestones like walking. This is a sign she is succeeding. Prenatal treatment can prevent organ damage. and improve babies’ lives, researchers report November 9 in the New England Journal of Medicine.
“It’s a great step forward,” says Bill Peranteau, a pediatric and fetal surgeon at the Children’s Hospital of Philadelphia who wasn’t involved in the work.
Rare condition called infantile-onset Pompe disease affects less than one in 138,000 worldwide born babies. It’s caused by genetic changes that either reduce levels of an enzyme called acid alpha-glucosidase, or GAA, or prevent the body from making it at all.
Inside cellular structures called lysosomes, GAA turns the complex sugar glycogen into glucose, the body’s main source of energy. Glycogen can build up to dangerously high levels without GAA. This can cause damage to muscle tissue including the heart and muscles that support breathing.
While some people can develop Pompe disease later in life or have a less severe version that doesn’t enlarge the heart, Ayla was diagnosed with the most severe form. Her body doesn’t make any GAA. Replacing missing enzymeInfusions can be used to reduce glycogen buildup. This is especially true if the infusion is started soon after birth.SN: 4/26/04).
Early studies with mice suggested that Pregnancy treatmentIt was promising in controlling Pompe-like diseases. Jennifer L. Cohen, a pediatric geneticist at Duke University School of Medicine, and her collaborators launched an initiative called “An Initiative to Control Pompe-like Disease.” Early-stage clinical trialCovering Pompe and seven other similar conditions, commonly known as lysosomal stock diseases.
Ayla was 24 weeks old when the team infused GAA through her umbilical vein. A total of six infusions were given to her mother, one each two weeks. Ayla was born with weekly infusions by the medical team. She will need them throughout her life.
Cohen states that both mother and child were safe with the therapy. But until more patients are treated and monitored in the trial, it’s unclear whether this prenatal enzyme replacement is always a safe and effective option. So far, two other patients with other lysosomal storage diseases have received treatment in the trial, but it’s too early to know how they’re faring.
Researchers are also looking into in utero treatments for rare genetic diseases such as the Blood disorder Alpha Thalassemia. Researchers also identified three children in 2018 who were described as Successfully treated for a sweating disorderThey were not yet born.
Peranteau believes that such approaches could be used to treat rare diseases in the future. However, it is crucial to show safety and efficacy of any new treatments after birth before they can be used in utero.
For now, it’s unclear how Ayla and other treated patients will fare over the long term, Cohen says. “We’re cautiously optimistic, but we want to be careful and be monitoring throughout the patient’s life. Especially those first five years, I think, are going to be critical to see how she does.”
