When Newborn Screening Catches a Deadly Genetic Disease

The leading genetic cause of infant death doesn’t necessarily reveal itself at birth. Here’s how one family still got the diagnosis in time.

In partnership with Novartis Gene Therapies, Inc.

While many will remember the second week of March as the last days before the COVID-19 pandemic lockdown began across the country, Kathryn McBride will remember it as a monumental event for a different reason: the birth of her twins, Conor and Tierney. “They were born at 11 a.m.—my husband was at work and got there a minute before they were born,” she recounted. Though the babies were 34-week-old preemies, they were big (6.5 pounds) and their vital signs were good.

Overnight, life turned upside-down for everyone. Outside of McBride’s hospital room, states began shutting down stores, schools, restaurants, and any business not considered essential, due to the pandemic. Inside, Kathryn was left alone since her husband, John, was not allowed back in to see her and the twins. “It was awful,” she said. “They wouldn’t even let you walk down the hall.” Pandemic aside, things soon took a turn for the worse when they received the results from their opt-in newborn screening test, revealing a genetic disorder that would impact one of her babies.

The Optional Newborn Screening Test That Saved Conor’s Life

In the days after the twins were born, Kathryn would make two trips a day up to the NICU where her preemies were being monitored. Because of her high blood pressure, the nurses would push her in a wheelchair to the nursery and Kathryn would spend an hour with her twins before being returned to her room. She was waiting to go up one afternoon when a nurse called and said the neonatologist wanted to speak with her.

Kathryn immediately sensed the news was not good, and once in the nursery, the neonatologist didn’t mince words. “She told me, ‘Your son has spinal muscular atrophy (SMA),’” said Kathryn. “I just looked at her — I was clueless. I had no idea what it was. In fact, I didn’t even remember opting into the newborn screening testing.”

Fortunately for Conor, she did. Millions of babies across the country routinely undergo newborn screening at birth for conditions that can affect a child’s long-term health or survival, but screening rules and which conditions are included in the panel vary by state. In 2018, SMA was added to the Recommended Uniform Screening Panel (RUSP), a federal list of often devastating disorders that require intervention as early as possible and have treatment options available.

Despite the fact that there are now treatments approved by the U.S. Food and Drug Administration (FDA) for SMA, not every state includes SMA as part of their routine newborn screening. In Massachusetts, where the McBrides live, expecting couples have the option to include SMA in their child’s newborn screening panel. Kathryn opted in—a decision that likely changed the course of her son’s life.

“It is critically important to identify and treat spinal muscular atrophy as early as possible and therefore, newborn screening has totally changed how we treat this disease, ” said Dr. Meredith Schultz, the executive medical director and head of translational medicine for Novartis Gene Therapies. “This allows us to treat patients even before they are showing any symptoms of SMA.”

Learning About SMA

Babies with SMA are born without a functional survival motor neuron 1 gene (SMN1), a gene that is responsible for producing SMN protein for the motor neurons that drive everything from sitting to swallowing to breathing.

“Motor neurons are powered by SMN protein. Without it, the motor neurons die, and this results in progressive weakness and paralysis of the muscles that control the body,” said Dr. Schultz. “Once the nerves in the spinal cord that go to our muscles are lost, we can’t get them back.”

There are four types of SMA. Which one an infant has is determined by the number of so-called “backup gene,” or survival motor neuron 2 (SMN2) gene, that are present. The fewer copies you have, the more severe the disease. About 60 percent of babies with SMA are Type 1, one of the most severe forms of the disease where usually just one or two copies of the backup gene are present. Left untreated, 90 percent of these infants died or needed permanent ventilation by their second birthday.

Fortunately, Tierney did not have SMA, the doctor told Kathryn. But with Conor, they soon found out he had Type 1 and that they would need to act fast to give him the best chance for survival. “At that point, I kind of blacked out,” she said. “She was saying a lot of stuff and I just lost it. I couldn’t handle it anymore. I had to leave the nursery.”

Alone in her room, she struggled to find a way to tell John. “I had to call my husband over the phone, which was awful,” she said. “His initial reaction was to be calm — he was trying to be strong because he knew I was still sick and in the hospital.” If this had to happen, we’re in the best city in the world for it, he reminded his wife, a nod to Boston’s multiple world-class medical facilities.

Getting the Help They Need

Meanwhile, the wheels were in motion to get Conor treatment. The pediatric medical team contacted a specialist at another local hospital who had experience with SMA and could set Conor up with a treatment plan to stop the loss of motor neurons. But it would mean separating Conor from his mother and also his twin — and in the early, unknown days of the pandemic contact would be severely limited. “The most difficult thing was that Conor looked completely normal,” said Kathryn, explaining that he was a preemie and was pre-symptomatic when he was born. “There was no evidence anything was wrong,” she said. “He seemed fine, which made this really hard to understand.”

Nevertheless, the neonatologist was adamant that Conor needed to be taken immediately for treatment since every passing day, he was losing motor neurons. “I just said, ‘Do it,’ because I knew we had no other choice,” Kathryn admitted. “If we waited, who knew what would happen because of COVID?”

At the age of five days, little Conor was sent via ambulance to receive treatment. Under the care of one of the world’s top neurologists and geneticists specializing in SMA, he started a chronic treatment. Conor’s neurologist told Kathryn that because Conor was premature, he was not eligible to receive a one-time therapy called ZOLGENSMA® (onasemnogene abeparvovec-xioi). But the McBrides preferred a one-time treatment for Conor – so once he reached gestational age, they completed additional testing which confirmed he would qualify for the treatment.

Zolgensma, approved by the FDA in 2019, is a one-time gene therapy for children under the age of two. Zolgensma is the only therapy that addresses SMA at its genetic root cause by replacing the function of the missing or non-working SMN1 gene with a single, one-time IV infusion.

“With Zolgensma, we’re replacing the function of the missing gene so the body can make more of the missing SMN protein,” said Dr. Schultz.

Every patient’s treatment journey is different. Families and their physicians need to consider both the potential benefits and potential risks of each treatment when making treatment decisions.

Zolgensma has a risk of acute serious liver injury, and in clinical trials the most common side effects were elevated liver enzymes and vomiting. Please continue reading for additional Important Safety Information below and please see the accompanying Full Prescribing Information.

In June of 2020, Kathryn and John brought three-month-old Conor to the pediatric infusion clinic to receive Zolgensma. After such a dramatic build-up, the treatment itself was remarkably stress-free. “It was so easy,” Kathryn said. “We just sat there and I held him. We waited a little bit after to make sure he had no reaction to the gene therapy.” When Kathryn asked the medical team what comes next, she was told by the medical team she had to watch and wait. As per the Zolgensma prescribing information, Conor received an oral corticosteroid starting the day before infusion, which is then continued after infusion for about two months or longer depending on liver function labs and clinical exams. Children need weekly, bi-weekly, and then monthly blood tests for at least the first three months following treatment.

After both of his treatments and physical therapy, Conor was achieving his milestones, something Kathryn wasn’t sure she would ever see – even with Conor’s early diagnosis and pre-symptomatic treatment. He was kicking his legs more, she realized, and his energy levels rose.

“Conor’s physical therapist told me, ‘If I didn’t know he had SMA Type 1, I would never think he had it—he seems completely normal,’” said Kathryn.

It Started with a Heel Prick

Today, 14-month-old Conor is a cuddly bundle of joy and enthusiasm. He loves the outdoors, dogs, and leaves blowing on trees on a windy day. His ability to hit motor milestones gives Kathryn and John hope for a full and active future for their son. As if eager to prove them right, in home videos, Conor can be seen bopping around in his crib and vigorously crawling across the floor—moments Kathryn and John weren’t certain would ever come.

It’s exactly because of Conor’s positive prognosis that Kathryn feels an urgency to let other parents know about the importance of including SMA in the newborn screening program in every state. “If it’s available, you need to get it done,” she said. “Don’t be afraid of what you might find out. It’s worse to find out down the road.”

It’s also critical that parents take an active role in getting help if the newborn screening tests turn up something unexpected. “Trust the doctor and move quickly,” she said. “Time is of the essence with these babies. The sooner they can be treated for SMA, the better. Yes, it’s scary putting your trust in people you don’t know, but the alternative of delaying treatment is far, far worse.”

Results and outcomes vary among children based on several factors, including how far their SMA symptoms had progressed prior to receiving treatment.

Indication and Important Safety Information for ZOLGENSMA® (onasemnogene abeparvovec-xioi)


ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time infusion into a vein. ZOLGENSMA was not evaluated in patients with advanced SMA.

What is the most important information I should know about ZOLGENSMA?

  • ZOLGENSMA can cause acute serious liver injury. Liver enzymes could become elevated and may reflect acute serious liver injury in children who receive ZOLGENSMA.
  • Patients will receive an oral corticosteroid before and after infusion with ZOLGENSMA and will undergo regular blood tests to monitor liver function.
  • Contact the patient’s doctor immediately if the patient’s skin and/or whites of the eyes appear yellowish, or if the patient misses a dose of the corticosteroid or vomits it up.

What should I watch for before and after infusion with ZOLGENSMA?

  • Viral respiratory infections before or after ZOLGENSMA infusion can lead to more serious complications. Contact the patient’s doctor immediately if you see signs of a possible viral respiratory infection such as coughing, wheezing, sneezing, runny nose, sore throat, or fever.
  • Decreased platelet counts could occur following infusion with ZOLGENSMA. Seek immediate medical attention if the patient experiences unexpected bleeding or bruising.
  • Thrombotic microangiopathy (TMA) has been reported to occur approximately one week after ZOLGENSMA infusion. Caregivers should seek immediate medical attention if the patient experiences any signs or symptoms of TMA, such as unexpected bruising or bleeding, seizures, or decreased urine output.

What do I need to know about vaccinations and ZOLGENSMA?

  • Talk with the patient’s doctor to decide if adjustments to the vaccination schedule are needed to accommodate treatment with a corticosteroid.
  • Protection against respiratory syncytial virus (RSV) is recommended.

Do I need to take precautions with the patient’s bodily waste?

Temporarily, small amounts of ZOLGENSMA may be found in the patient’s stool. Use good hand hygiene when coming into direct contact with bodily waste for 1 month after infusion with ZOLGENSMA. Disposable diapers should be sealed in disposable trash bags and thrown out with regular trash.

What are the possible or likely side effects of ZOLGENSMA?

The most common side effects that occurred in patients treated with ZOLGENSMA were elevated liver enzymes and vomiting.

The safety information provided here is not comprehensive. Talk to the patient’s doctor about any side effects that bother the patient or that don’t go away.

You are encouraged to report suspected side effects by contacting the FDA at 1-800-FDA-1088 or, or Novartis Gene Therapies at 833-828-3947.

Please see the Full Prescribing Information.

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US-ZOL-21-0193 08/2021