When their son Brody had a seizure at age 3, Molly and Matt Koslowski of DeForest were dismayed to learn he might have epilepsy.
Genetic testing brought a diagnosis even more dire: Brody had a rare condition, known as Batten disease, expected to take away his vision, movement and thinking ability, and end his life by age 6 to 8.
Then came opportunity and more adversity. A new treatment was available for Brody’s form of Batten, delivered biweekly through unusual infusions directly into the brain. A UW Health team traveled to Chicago to learn how to give it, allowing Brody, now 6, to be treated near home.
But this past December, shortly after Molly quit her teaching job to care for Brody and two younger sons, she got her own disheartening medical news. The 37-year-old has breast cancer, for which she is undergoing chemotherapy, also at UW Health.
“We already had his diagnosis. Why would I also have cancer?” Molly Koslowski said. “We can either curl up in a ball and cry, or we can fight and make the most of each day.”
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It was on a snow day in January 2019 when Molly, then a health teacher at Harvest Intermediate School in DeForest, and Matt, a science teacher at DeForest Area High School, first saw Brody convulsing. Matt was clearing snow from the front sidewalk and Molly was pulling Brody on a sled when the boy slumped backward and started shaking.
They took him to the emergency room, where tests confirmed a seizure. A week later, he had a second one. Doctors prescribed medications for seizures, with mixed results. Brody also had delayed speech, which suggested something else might be going on.
Dr. David Hsu, a pediatric neurologist at UW Health, recommended genetic testing. It found Brody has an inherited brain disorder called neuronal ceroid lipofuscinosis type 2, or CLN2, one of 14 forms of what is collectively known as Batten disease. Batten affects an estimated 2 to 4 of every 100,000 children in the U.S., according to the National Institutes of Health.
At first, the Koslowskis didn’t know how the diagnosis was possible. They used an egg donor to conceive Brody, and the donor was a carrier of some type of rare gene mutation, they recalled. But Matt’s testing at the time was clear, meaning he wasn’t a carrier. For a child to have Batten, both genetic parents must be carriers.
After Brody was diagnosed, Matt was tested again and found to carry an especially rare mutation for CLN2 that hadn’t been picked up by his earlier testing, the couple said. When both parents are carriers, each child has a 25% of having the condition and a 50% chance of being a carrier.
The Koslowski’s second child, Colton, 3, conceived prior to Brody’s diagnosis using the same egg donor, is a carrier for Batten but doesn’t have the disease. Their third child, Jack, who turns 1 on Tuesday, was conceived by Molly and Matt in what Molly called a “pandemic surprise.” He is not a carrier.
Treatment in Madison
When Hsu learned about Brody’s CLN2 in May 2019, he knew that two years earlier the Food and Drug Administration had approved the first and only drug for any form of Batten. The drug, an enzyme replacement therapy called cerliponase alfa, or Brineura, by Biomarin Pharmaceutical Inc., is only for CLN2. It can slow or halt, but not reverse, the progression of symptoms.
Only a few centers were administering the drug. It costs more than $700,000 a year and is invasive, requiring a port to be implanted in the skull and infusions lasting four hours every two weeks. Wisconsin is expected to see a child with CLN2 only about once every two years, so patient volume for an infusion program would be low.
Despite the challenges, Hsu and others at UW Health decided to provide the treatment. He, three other doctors and two nurses went to Rush University Medical Center in Chicago, where Brody got his first infusion in June 2019, to observe.
By the time Brody needed his second infusion, the UW Health team was able to give it to him in Madison. His treatment is covered by the Koslowskis’ private insurance and Wisconsin’s Medicaid program.
“It’s one of the most horrible diseases we have to deal with,” Hsu said, explaining his motivation for providing Brineura. “The life goes out of their eyes. They just sit there. Sometimes they have really bad seizures, which we have a hard time controlling. Then they die.”
Pursuing such treatments, despite the considerable cost, can improve and prolong life while enabling more scientific progress, Hsu said. “It’s a matter of what you think is worthwhile,” he said. Brody “certainly enjoys his life. His parents enjoy him.”
Unlike most infusions delivered through a port in the chest, Brineura is given directly into the fluid-filled ventricles of the brain. That way, the treatment can bypass the blood-brain barrier, a layer of cells that keep out foreign substances.
The dexterity required to get the needle in the right spot to access the port, especially in a wiggly, nonverbal boy who is sensitive about people touching his head, is not to be underestimated.
“It has taken us a lot of practice to be able to do it on one poke,” said Alexa Beversdorf, a nurse practitioner who did the procedure on Brody last month at UW’s American Family Children’s Hospital as Matt tried to hold his son still. “They’re moving targets.”
UW Health is providing Brineura to two other, younger children from the Milwaukee area. The children receive a calming medication beforehand but aren’t sedated, as that would be too risky to do frequently, Beversdorf said.
Advocates hope to get Batten disease added to the tests included in routine newborn screening so babies with CLN2 could be diagnosed and treated before developing symptoms, which might improve outcomes.
Dealing with two diagnoses
Brody, who has had 76 infusions over nearly three years, can still walk, with assistance. He has lost most of his vision, which makes him hesitant on his feet unless his parents are holding his hands, they said.
He doesn’t speak, but his parents said they have become attuned to his sounds and screams, and can understand what he needs.
He likes to swim, which led the Koslowskis to use some of the money raised by the community for Brody to buy a therapy pool to help him exercise after the COVID-19 pandemic temporarily shut down other swimming opportunities. He rides an adaptive bike, bounces on a trampoline and enjoys listening to movies, including “Finding Dory” and “Ice Age.”
Brody got a feeding tube last year, but it’s mostly used for medications. Molly or Matt typically hand-feed him small pieces of food, in part to help maintain his chewing and swallowing abilities. “If he uses it, he’s not going to lose it as quickly,” Matt said.
As Brody approaches his seventh birthday in July, the Koslowskis have ordered a walker and wheelchair for him and a wheelchair-accessible van. They removed carpet and installed vinyl flooring in their home so he can move around more easily.
“He’s still here and he’s still kind of functioning,” Molly said. “He should be a vegetable, but he’s not.”
After she learned four days after Christmas that she has breast cancer, Molly started chemotherapy in January. She expects to get a double mastectomy this summer and eventually have her ovaries removed. She has a BRCA1 gene mutation that greatly increases the risk of breast and ovarian cancers.
After her diagnosis, Matt went on medical leave to help take care of the family. Even so, keeping track of Brody’s medications, supplies and appointments, along with managing the younger boys and dealing with Molly’s fatigue-inducing cancer treatments, can be a challenge.
“I should be taking care of myself,” Molly said. “But I can’t. I still have (Brody) and the other two that need me.”
Hsu said Brody’s future is hard to predict, but he’ll likely outlive the window of age 6 to 8 the doctor initially shared with the Koslowskis. “I have hopes he could go many years,” Hsu said.
Molly said treating Brody with the infusions is “helping provide him with the best quality of life we possibly can.”
The family’s medical challenges are helping her and Matt to “embrace each day and opportunity,” she said. “Simple things like going for a nice walk as a family of five mean so much to us.”
No time to lose: Finding rare diseases in infants
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