When Getting the Right Diagnosis Is Half the Battle
Their daughter was born with a rare genetic disorder, but before Annie and Joe could get her treatment, they’d have to advocate for a diagnosis
In partnership with Novartis Gene Therapies, Inc.
Looking back, there were little signs. Not being able to push up into the crawl position. An unwillingness to bear weight on her feet when held in a standing stance. A diminishing appetite. Ironically though, the biggest tip-off that something was wrong with eight-month-old Quinn wasn’t one of these typical milestones seen between the six- and nine-month check-up or outlined in any parenting book. “She would do this little jiggly dance when she was lying down that I’d never seen before,” recalls her father, Joe Wiseman. “It was this kind of floppy move. None of her three older siblings had acted that way.”
For the most part though, Joe and his wife Annie didn’t think much of their infant’s slowness to hit certain developmental milestones in the first half-year of her life. Quinn could roll over; she could sit up. The rest? “We just figured she was taking her time — she was the youngest child,” Annie says. With the reassurance of their pediatrician, they refused to judge the newest member of their family too harshly against the textbook markers for motor skill development, even though baby videos of the couple’s three older children suggested Quinn’s development was significantly slower.
In 2019, Joe and Annie took Quinn and her siblings to visit family in Utah. “My mom’s next-door neighbor is a doctor,” says Annie. “When he picked up Quinn, he turned to me and said, ‘You guys have to quit holding her so much—this baby is nothing but fluff.’” Another parent might have laughed and brushed it off. But for Annie and Joe, these words struck a nerve, the culmination of fears they’d both been reluctant to verbalize. Something was wrong with their little girl. But what?
Uncovering the Truth
At Quinn’s nine-month checkup, Annie pressed her pediatrician over what could be wrong. “I told him she’s not crawling, she’s not bearing weight on her legs, she won’t stand,” says Annie. They got Quinn a bouncer, as the doctor suggested, and tried to get her to use her legs.
Panic began to set in — first that low-grade sense something was off, then an escalating feeling of parental fear that if they didn’t help their daughter, something terrible would happen. “My wheels started turning,” says Annie. “My mommy intuition was just — okay, there’s something going on.”
After listening to the advice from one of their other children’s teachers, Annie and Joe arranged for a physical therapist and child developmental specialist to come for a visit. After an hour-long evaluation, they had one thing to say: Quinn needed to see a neurologist immediately. “Everything about the way she moved and how her body was, they were just like, red flag, red flag, red flag,” says Annie.
There was something else they said that grabbed Joe’s attention. “They kept telling us, ‘She has a lot of hypotonia,’” he remembers. “I had no idea what that meant, so as soon as they left, I just turned into a research wizard and started Googling everything I could find.”
It turned out that hypotonia, the clinical term for low muscle tone, was affiliated with several diseases, including spinal muscular atrophy, or SMA. “I recognized the name because my friend’s son has SMA Type 1,” Joe says. But that child, years earlier, had nearly died as an infant and was now on feeding tubes. It was hard to reconcile the image of him with their bubbly baby.
In his ongoing research, Joe found videos of babies with SMA Type 2. “It felt like I was literally watching videos of my daughter.” The way the babies positioned themselves, the way they moved, but especially “this weird little shimmy they do with their bodies — this kind of dance,” he says. “It’s like they have jelly in the middle.” Beyond a doubt, Joe believed his daughter had SMA Type 2. So, now what?
SMA is a rare, devastating disease that affects about one in 10,000 babies born and is a leading genetic cause of infant death. Most babies with SMA are born with a missing or nonworking survival motor neuron 1 gene (SMN1), which is responsible for the development of motor neurons in the body that control virtually all physical movement. Babies with SMA experience the rapid and irreversible loss of motor neurons, affecting muscle functions like breathing, swallowing, and basic movement.
“SMA progresses quickly, and once a patient loses motor neurons – the cells that make our body move – they cannot get them back,” said Dr. Meredith Schultz, the executive medical director and head of translational medicine for Novartis Gene Therapies.
There are four main types of SMA, each of which is based on the age that symptoms begin and the highest physical milestone achieved.
Babies with SMA Type 1, one of the most severe types, typically have just one or two copies of SMN2. Although SMN2 copy numbers are correlated with SMA type, the classification of SMA types are not based on SMN2 copy numbers (i.e. some patients with two copies can have Type 2 if they achieve sitting). If left untreated, they will experience rapid and irreversible loss of motor neurons, and 90 percent will die or require permanent ventilation by age two. Babies with SMA Type 2 typically have three to four backup copies of the gene and are usually diagnosed between six and 24 months of age.
“SMA Type 2 is usually harder to diagnose in babies because they are developing, they are reaching all the motor milestones at first and then around six or so months, they plateau or start to regress,” said Dr. Schultz. “They may show no interest in putting weight on their legs or may stop trying to pull themselves up. It’s different than SMA Type 1 where a baby might have low muscle tone or issues breathing early on.”
The day after the early intervention visit, Joe and Annie brought Quinn back to see their pediatrician, who sought insurance authorization for the genetic test that could determine if Quinn had SMA. He also agreed to help her get in to see a pediatric neurologist to help with next steps.
But through his research, Joe could hear the clock ticking. With every passing week, studies show, babies with SMA lose motor neurons they can never get back. Treatment as soon as possible is critical.
“The sooner, the better when it comes to diagnosing and treating SMA,” explained Dr. Schultz. “The earlier SMA is diagnosed, the sooner a patient can start treatment and halt the disease progression so more motor neurons are not lost. I’ve worked with SMA patients for years, and any delays in diagnosis can impact the health outcomes for these patients.”
If there was a silver lining to the events, it was receiving news the following day from Quinn’s pediatrician that the insurance company had approved the genetic test.
The results confirmed what Annie and Joe already knew in their hearts: Quinn had SMA Type 2. “From there it was warp speed,” says Joe. They were connected with a neuromuscular specialist at a hospital in New Mexico who discussed available treatment options and helped the family learn more about Zolgensma® (onasemnogene abeparvovec-xioi), a gene therapy used to halt the progression of SMA.
“Zolgensma is the only treatment that addresses the genetic root cause of SMA by replacing the missing or nonworking SMN1 gene,” explained Dr. Schultz. “It replaces the missing or non-working SMN1 gene with a functioning copy and allows the body to produce the necessary protein those motor neuron cells need.”
Approved by the U.S. Food and Drug Administration (FDA) in May 2019, Zolgensma, a one-time treatment, is the only gene therapy available to treat the disease. It is approved by the FDA for children under the age of two, meaning if Joe and Annie waited much longer, Quinn would no longer be a candidate for treatment. “We felt Zolgensma was our best hope for Quinn,” says Annie. 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 see additional Important Safety Information below and accompanying Full Prescribing Information.
The day before Thanksgiving in November of 2019, at around 14 months old, Quinn received the one-time hour-long infusion. Before and after the Zolgensma infusion, she received an oral corticosteroid. All children treated with Zolgensma need to receive an oral corticosteroid starting the day before infusion, and then after infusion for about two months or longer depending on their liver function exams and labs. In addition, baseline and follow-up tests are required for at least three months post-infusion.
“It was a surreal day,” says Joe. “After all this build-up, here she was sitting in a hospital bed with an IV in each arm and this little tube. It only took an hour. The doctors and pharmacists were there and everyone had these big grins on their faces. I could see Quinn looking back at us, like ‘What is going on?!’”
Following her Zolgensma treatment, Annie and Joe patiently waited to see if the treatment would work. Then, one day, Annie put Quinn in a crawling position on the floor. And for the first time in her life, Quinn held it all on her own. She even raised her head. It was a sign, says Joe. There was a light at the end of the tunnel. In clinical trials, improvement in motor function was seen as early as one month post-infusion.
In the 16 months since she received Zolgensma, Quinn has made steady progress in gaining new motor skills. Like other children treated with Zolgensma, Quinn returned for blood tests weekly, bi-weekly, and then monthly for the first several months following treatment. Those tests are behind them now, and the trajectory is onward and upward.
“I do wonder sometimes, what’s school going to look like for her? What will friendships look like for her?” says Annie. “I have little panic attacks here and there, just wondering about how her life is going to be different than her siblings. But she’s an incredibly resilient and happy toddler. It’s going to be OK.”
A year and a half after their journey began, Annie and Joe are home with their kids, in the midst of afterschool games and adventure-making. From the other room, Quinn, now two and a half, emits a shriek that would set most parent’s radars on high alert. Joe just laughs. “See how good she can yell now?” he says. “I say that as a joke, but I’m being serious — it’s a reminder of how far she’s come because she never had the strength to be that loud before. She can scream with the best of them now.”
By sharing their journey, Joe and Annie hope that all parents will learn to advocate for their children. “The first thing we learned from our experience, and this is so important to me, is never, ever doubt your parental intuition,” said Joe. “If it’s in your gut, don’t stop searching for answers.”
Quinn is crawling on her own. She can hold herself up, and with Annie’s careful supervision, move her legs forward in the right direction. With the help of leg braces, she can stand at her easel and color, one of her favorite activities. She has a play kitchen in the backyard that provides hours of entertainment and a passion for Play-Doh and Calico Critters. Quinn is a happy toddler, learning to fend for herself with three boisterous older siblings.
“She loves to dance,” says Annie. “She will lie on her back and kick her legs and say, ‘I’m a ballerina.’ We hope one day, she will get there.”
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)
What is ZOLGENSMA?
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 www.fda.gov/medwatch, or Novartis Gene Therapies at 833-828-3947.
Please see the Full Prescribing Information.
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