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Marley, 6, was the only person with this rare genetic condition – and now her family has hope

Since Marlene Berthoud was diagnosed as the only person with the genetic condition, doctors have identified more children and found a potential treatment.
/ Source: TODAY

Since Marlene “Marley” Berthoud’s birth in 2015, something was wrong with her health. For years, her parents weren’t sure what. Then they learned that Marley had a condition so rare that she was the only person with it. While they felt relieved finally having an answer, they also grappled with overwhelming emotions — love, guilt, confusion, isolation and uncertainty.

But in November 2019, life offered some certainty when Marley started receiving a drug that eased some of her symptoms. And, the little girl is paving the way for the others who have since been diagnosed with this condition caused by a mutation on the ornithine decarboxylase 1 gene.

When Marley was born, thick silvery blonde hair covered her head. When it started falling out, doctors and her parents worried it was sign something was wrong.Courtesy Berthoud family

“We have seen outstanding results with the change in her abilities,” Kelly Berthoud, Marley’s mom, 38, a registered nurse in Kalamazoo, Michigan, told TODAY. “When we were presented with (the treatment) it was like, ‘It might work.’ That was probably the hardest decision to make because nobody had done it before. As a parent, you don’t want to harm your children or make the wrong decisions … I’m so glad we took the first step.”

A collection of symptoms leads to a one-of-a-kind diagnosis

When Berthoud gave birth to Marley at 37 weeks, doctors noticed immediately that she was unique. She had a shock of silvery blonde on her head, which was too large. And Marley couldn’t regulate her temperature or blood sugar and struggled to suck or swallow, which most infants are born knowing how to do. An MRI showed that Marley had two brain hemorrhages and she experienced developmental delays. Suddenly she lost all her hair, including eyebrows and eyelashes. Still, Marley’s symptoms didn’t match any known condition.

“Our neurologist was like, ‘Something was not fitting in with her. Something wasn’t right,” Berthoud told TODAY in 2018. “There was a long period thinking about what we have and how to move forward without a lot of advice from the medical community.”

Immediately after Marley Berthoud was born, doctors knew there was something wrong with her. But it took three years to discover the girl was the first diagnosed with a new genetic disorder.Courtesy Berthoud family

Their neurologist recommended genetic testing and that’s when the family met Dr. Caleb Bupp, a medical geneticist at Helen DeVos Children’s Hospital in Grand Rapids, Michigan. He, too, felt baffled by the symptoms. After several tests he detected a mutation on ODC1, but this wasn’t linked to any existing illness.

“She had her own syndrome,” he told TODAY in 2018. “Even though the Berthouds have an answer, it didn’t change things.”

At first, life for the Berthouds remained the same. Then Bupp heard a presentation from André Bachmann, a professor of pediatrics at Michigan State University College of Human Medicine. Children with brain cancer produce too much ODC and there’s a drug that reduces it. Bupp had a “lightbulb” moment when he wondered if this could help Marley. The two researchers started working together and are humbled that their collaboration might help those with the ailment, now called Bachmann-Bupp syndrome.

In 2018, Marlene “Marley” Berthoud became the first person diagnosed with what's now called Bachmann-Bupp syndrome. About a year ago, she started treatment and has been blossoming ever since. Courtesy Spectrum Health

“We don’t want any patient, like Marley, to have this condition. But if a situation like this arises and we are able to find a drug to help her, this, from a scientific point of view, is the absolute dream come true,” Bachmann told TODAY. “Many scientists can never claim that they have discovered something ... at the very beginning and have a treatment for it.”

Treatment and community

A month after Marley, now 6, started treatment, her eyelashes and eyebrows grew back. Soon, her hair regrew on her head. By March 2020, she sat up by herself for the first time.

“We’re starting to see a lot of improvement with her muscle tone and her coordination and her ability to move around. It’s been an ongoing progression of her abilities and now she’s about to scoot around the house,” Berthoud said. “She likes to find troublesome things to get her brother into trouble with — or try.”

Marley also babbles and communicates using sign language, often asking for more crackers. The family is thrilled with Marley’s transformation.

“It’s pretty incredible … watching her grow and meet all these milestones,” Berthoud said.

Since starting the treatment, Marlene “Marley” Berthoud has blossomed. She's learning sign language to communicate and often asks her parents for crackers. That is when she's not trying to encourage her younger brother to get into trouble. Courtesy Spectrum Health

The drug, used to treat some children with cancer and people with African sleeping sickness, works by suppressing the gene OCD1.

“Her (mutation) — and the (mutation) we’ve seen now in ... some of these other patients — it actually moves the gene into overdrive,” Bupp told TODAY. “You can try to cool the system down with a drug instead of having to replace or fix it … You get rid of the excess gene product.”

Bupp said this is somewhat unusual in genetics.

“It doesn’t happen a lot,” he said. “We got really lucky that this disease hits in such a place that you can actually do something about it. What we saw was that the abnormalities and the biochemistry that were caused by this gene mutation actually all got better when we started the drug.”

Marley was able to receive the drug through the single patient investigational new drug application from the U.S. Food and Drug Administration.

After about a year of treatment, the researchers applied for use on another child, Jameson Jibben, 6. He had his first dose last week. Jameson’s parents learned about Bachmann-Bupp syndrome and treatment after mom Kayla Jibben read about Marley. She thought they were alike because the two shared some commonalities: Jameson was also born with long dark hair and had an unusual collection of symptoms.

“There was the hair failing out. He has a large head,” Jibben, 32, told TODAY. “He had holes in his heart — just things that didn’t really fit with a specific genetic syndrome.”

Jameson underwent whole genome genetic testing twice and they went to the Stanford Center for Undiagnosed Diseases in the fall of 2019 and in June 2020 they had a diagnosis. Jibben reached out to Berthoud for support and learned about the treatment, which he’s receiving from Bupp in Michigan.

“It wasn’t until I saw pictures of Marley looking so similar to Jameson is when it really hit me that, ‘Wow, we’re not alone in this. There’s someone almost exactly like Jameson,’” she said.

Marlene “Marley” Berthoud's family loves seeing their daughter transform thanks to a medication she's receiving to treat the ultra rare condition she has. Courtesy Spectrum Health

The Berthouds felt grateful for the connection.

“It was mind-blowing that there’s somebody else in the world that has a child like mine,” Berthoud said. “When you’re the only one in the world it is very isolating and when Kayla reached out to me it was like … ‘Now I have another person.’”

It’s too soon to know how the drug will work in Jameson and Jibben said they watch excitedly in hopes they’ll detect a change in him immediately. They’re hoping they’ll get to experience what the Berthouds have as they watch their daughter blossom.

“Before we started treatment, Marley was very infantile,” Berthoud said. “She (now) has abilities to investigate her world and learn about her environment. She’s all about it, so inquisitive.”