First child with ODC-1 genetic disease receives treatment

Since Marlene “Marley” Berthoud was born in 2015, something was wrong with her health. For years, his parents didn’t know what. Then they learned that Marley had such a rare disease that she was the only person to suffer from it. While they felt relieved to finally have an answer, they also struggled with overwhelming emotions – love, guilt, confusion, isolation and uncertainty.

But in November 2019, life offered some certainty when Marley began receiving medication that relieved some of her symptoms. And, the little girl is leading the way for others who have since been diagnosed with the disease caused by a mutation in the ornithine decarboxylase 1 gene.

“We have seen tremendous results with the change in her abilities,” said Kelly Berthoud, mother of Marley, 38, a registered nurse in Kalamazoo, Michigan today. “When we were introduced to (the treatment) it was like, ‘It might work. It was probably the hardest decision to make because no one had done it before. As a parent you don’t want to hurt your kids or make bad decisions… I’m so glad we took the first step.

A set of symptoms lead to a single diagnosis

When Berthoud gave birth to Marley at 37 weeks, doctors immediately noticed that she was unique. She had a silver blonde shock on her head, which was too big. And Marley couldn’t regulate his temperature or blood sugar and had difficulty breastfeeding or swallowing, which most infants born can do. An MRI showed Marley had two brain hemorrhages and had developmental delays. Suddenly she lost all of her hair, including her eyebrows and eyelashes. Still, Marley’s symptoms did not correspond to any known condition.

“Our neurologist thought, ‘Something was wrong with him. Something was wrong, “said Berthoud TODAY in 2018.” There has been a long period of reflection on what we have and how to move forward without a lot of guidance from the medical community.

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

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

At first, the life of the Berthouds remained the same. Next, Bupp heard a presentation from André Bachmann, professor of pediatrics at Michigan State University College of Human Medicine. Children with brain cancer produce too much ODC, and there is a drug that reduces them. Bupp had a “light bulb” moment when he wondered if this could help Marley. The two researchers have started working together and are honored that their collaboration can help people with the condition, now known as Bachmann-Bupp syndrome.

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

Treatment and community

A month after Marley, now 6, started the treatment, her eyelashes and eyebrows have grown back. Soon her hair grew back on her head. In March 2020, she sat on her own for the first time.

“We’re starting to see a lot of improvements in his muscle tone, coordination and ability to move. It has been a continuous progression of her abilities and now she is about to take a tour of the house, ”said Berthoud. “She likes to find awkward things to get her brother in trouble – or to try.”

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

“It’s pretty amazing… to see her grow up and reach all these milestones,” said Berthoud.

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

“Its (mutation) – and the (mutation) that we’ve seen now in … some of these other patients – that causes the gene to overdrive,” Bupp said TODAY. “You can try to cool the system with a drug instead of having to replace it or fix it… You are getting rid of the excess genetics.”

Bupp said it’s somewhat unusual in genetics.

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

Marley was able to receive the drug thanks to the U.S. Food and Drug Administration’s single-patient investigational new drug application.

After about a year of treatment, the researchers requested use on another child, Jameson Jibben, 6. He received his first dose last week. Jameson’s parents heard about Bachmann-Bupp syndrome and its treatment after his mother Kayla Jibben found out about Marley. She thought they looked alike because the two shared similarities: Jameson was also born with long dark hair and exhibited an unusual collection of symptoms.

“There was hair falling out. He’s got a big head, ”Jibben, 32, said TODAY. “He had holes in his heart – just things that didn’t really correspond to a specific genetic syndrome.”

Jameson underwent whole genome genetic testing twice and they attended the Stanford Center for Undiagnosed Diseases in the fall of 2019 and in June 2020 they were diagnosed. Jibben asked Berthoud for help and learned of the treatment he is receiving from Bupp in Michigan.

“It wasn’t until I saw pictures of Marley looking so much like Jameson that I really understood, ‘Wow we’re not alone in this case. There’s someone almost exactly like Jameson,’ she declared.

The Berthouds felt grateful for the connection.

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

It is too early to know how the drug will work in Jameson, and Jibben said they were watching excitedly in the hopes that they would immediately detect a change in him. They hope they can find out what the Berthouds have by watching their daughter blossom.

“Before starting treatment, Marley was very infantile,” said Berthoud. “She (now) has the ability to investigate her world and learn more about her surroundings. She’s all about it, so curious.