Yusuf was a healthy, active, smiling baby. Until, all at once, he was not.
It happened on an airplane. Irfan Patel and Farheen Mohamed had taken their son to India to visit family. Yusuf, then nine months old, charmed everyone. But on the flight back to the U.S., he began to struggle to breathe. Seizures racked him. His little body went limp.
“I thought he was gone,” Farheen says.
The plane made an emergency landing in Istanbul, and Yusuf was whisked to a hospital in a coma. When he at last began to recover some function, his parents flew him back to the U.S. for further assessment.
Within days, they received the diagnosis that would change all their lives forever: Yusuf had methylmalonic acidemia.
“The doctor came and told me this would be a lifelong challenge. She sat with me. She cried with me,” Farheen recalls. Farheen could hardly process the news: “You’re in shock.”
“The doctor came and told us this would be a lifelong challenge.”
There is no cure for MMA. To manage the symptoms, patients go on a severely restrictive, low-protein, high-calorie diet, often through a feeding tube. Even so, they often experience life-threatening metabolic crises that can cause permanent neurocognitive damage.
Methylmalonic acidemia, or MMA, is a rare and life-threatening genetic disorder, affecting 1 in 25,000 to 50,000 newborns. A mutation in the MUT gene prevents the body from properly processing certain fats and proteins. As a result, toxic metabolites accumulate in the liver, in muscle tissue and in the brain. Symptoms include vomiting, lethargy, seizures, developmental delays and organ damage.
Read more about how LogicBio is working to help people living with MMA.
Yusuf is 16 now, and in some ways, he’s done remarkably well. He’s a freshman in high school who loves to play video games — especially Fortnite. Every Saturday morning, he makes omeletts for his family. (His specialty: Tomato and cilantro.) But there are also frustrations. His muscle tone remains weak and he can’t bike or play basketball. “It’s hard for him, because he wants to be accepted,” Farheen says.
He faces ongoing medical challenges. As a child, Yusuf was hospitalized nearly every month with severe infections or metabolic crises. At 10, overcome by fatigue, he received kidney and liver transplants. The transplants improved his quality of life; he has a bit more appetite and he’s allowed to eat treats like chocolate and ice cream in moderation. He’s still prone to infections, though, and cycles into the hospital every few months.
“I am told that I am special and I guess I am.”
“I try to spend my day as a normal kid, but it’s difficult to do things that come easy for other kids. Keeping up with daily meds, regular lab works and frequent hospital visits are very hard,” Yusuf says. “Sometimes I envy kids who do not have to worry about these things. The energy level and emotions are different each day.” Then he adds: “I am told that I am special and I guess I am.”
The Patels have three other children as well: Mariam, age 11, and Ibrahim, age 7, are healthy. Khadija, age 9, was diagnosed with MMA through prenatal screening.
Though Khadija has the same genetic mutation as her big brother, her childhood has been even more difficult. Put on a restricted diet at birth, Khadija maintained stable health for her first year. Then, suddenly, her system went haywire. For years, she was in the hospital nearly every month with metabolic crises.
As Irfan puts it: “We went through some very stressful periods.”
Two years ago, Khadija had a liver transplant. Since then, her metabolite levels have stabilized. But her muscle tone remains low. She’s very small for her age. And she’s well behind her peers in school. Yusuf takes charge of helping her with her homework. He plays with her, too, pushing his forehead against hers to stare her straight in the eyes — a game that makes her giggle with delight.
“Small things make her happy and small things make her sad,” Irfan says. “We don’t push her.”
The Patels, who live in suburban Delaware, have connected with other families dealing with MMA through the Organic Acidemia Association and online support groups. Irfan often tells parents that he’s learned not to plan, or even think, too far ahead. He knows from experience that MMA is unpredictable and precarious. “We just live in the moment,” he says.
Despite their frequent trips to the hospital, the Patels try to maintain family traditions, like visiting the zoo on lazy summer days. They even traveled to India this year to see relatives.
“What keeps me and my wife going is our two warriors,” Irfan says. “If they can get up every day and go about their days, why wouldn’t we?”
A surprise diagnosis
A few years ago, Irfan and Farheen got tested at the National Institutes of Health. Irfan was diagnosed with an exceptionally rare form of organic acidemia, a cluster of diseases that includes MMA. The researchers told him to be alert for potential neurological issues as he ages but couldn’t give him more specific advice. Only about a dozen cases of the same mutation have been reported in the scientific literature.
“I told my wife, ‘I’m sorry you married me when I carry this rare gene,” Irfan recalls. But for himself, he felt no sorrow. On the contrary: “When I was diagnosed, I was the happiest person on earth,” he says, “because I had something in common with my kids.”
Our development program:
LB-001 is an investigational, first-in-class pediatric genome editing therapy designed to save lives and prevent severe disabilities through early intervention. LB-001 uses GeneRide to incorporate a functioning version of the faulty MUT gene into the genome of MMA patients.