Katie Grace’s Story: Whole Genome Sequencing to Diagnose Leukodystrophy

Katie Grace’s early childhood in the charming city of Lexington, Kentucky was uneventful in all the best ways. It wasn’t until she was 4 years old that her parents, Meghan and Brian, noticed that she struggled with balance and fell a lot.

Meghan and Brian mentioned it at their next well-child checkup, and the pediatrician eased their concerns, saying it was just an age thing that Katie Grace would outgrow. While that proved true for Katie Grace’s peers, her clumsiness and frequent falls continued. 

The pediatrician thought the problem was low muscle tone, so he referred Katie Grace for physical therapy (PT). But after three months of physical therapy, the therapist told Meghan she thought there was something else going on.

“She said, ‘I think it might be something neurological,’” recalls Meghan.

From keen observation to leukodystrophy diagnosis

The family went to see the neurology team at a nearby children’s hospital. Results from an MRI there showed abnormal white matter on Katie Grace’s brain; the specialists suspected she had a form of leukodystrophy.

“I cried for four days straight,” says Meghan.

Leukodystrophies are rare genetic disorders with primary white matter abnormalities in the central nervous system. These disorders are a diagnostic challenge for most clinicians. The Leukodystrophy Center at Children’s Hospital of Philadelphia (CHOP) provides diagnostics, clinical care, and research opportunities to addresses the unique needs of infants, children and adolescents with inherited white matter diseases. The Center provides state-of-the-art laboratory and imaging diagnostics and integrated multidisciplinary care from top specialists across CHOP.

Experts in the Center are engaged in a number of studies focused on the diagnosis, characterization, and treatment of individual leukodystrophies. These research efforts include both clinical trials and natural history studies, with an aim toward developing new treatment approaches and potential cures.

The family was put in touch with the Center, and Katie Grace was enrolled in a study to evaluate if a form of genetic testing known as whole genome sequencing (WGS) is an effective tool to diagnose leukodystrophies. As part of the study, Katie Grace had blood drawn locally and sent to CHOP where it was put through the WGS process. Results from the test came back in early March of 2020, the week the world slowed to a halt from the COVID-19 pandemic.

Ongoing monitoring to ensure the best quality of life

Katie Grace has 4H leukodystrophy, a condition that often causes motor problems, including stiffness of the muscles and joints and problems with balance and coordination. Those with the condition can also have movement disorders, including tremor or difficulty controlling smooth movements of their arms and legs. They are also usually small for their age, and they do not go through typical puberty.

There is no known cure for 4H leukodystrophy, but treatment is available to manage symptoms and improve a child’s quality of life. Leukodystrophy Center Director, Adeline Vanderver, MD, oversees Katie Grace’s care, which includes follow-up appointments twice a year: once at CHOP and once a children’s hospital closer to the family’s home. Knowing Katie Grace has one of the world’s leading experts looking out for and ready to address any symptoms that cause discomfort as she grows gives Meghan great relief.

“They run that program like a well-oiled machine,” says Meghan of the Leukodystrophy Center. “We told ourselves from the get-go that none of us knows what the future holds but we are going to find out where the experts are and we’re going to go there. Knowing that we are going to a physician who specializes in this gives us an extraordinary amount of confidence. As much as you can have when you’re looking at such a rare condition.”

For now, Katie Grace’s leukodystrophy symptoms are very mild. She is 11 years old and, so far, hasn’t needed medication to treat her symptoms. She still does regular PT with the same therapist who made the game-changing observation that led to her leukodystrophy diagnosis. Dr. Vanderver expects to know more about how the condition will impact Katie Grace’s future trajectory when she reaches age 15 or so.

Katie Grace is doing great in school both academically and socially, says Meghan. She has an individualized education plan (IEP) that provides her extra time to transition from one activity to the next. But she doesn’t let her balance and stability issues hold her back.

“She is the grittiest kid I know,” says Meghan. “She does competitive cheerleading, she takes tumbling classes, and she does extraordinarily well given the obstacles. She loves competition.”

“When you get this type of diagnosis, it’s easy to feel like you are alone on a planet because it’s so rare,” adds Meghan. “I think it’s so important to hear other people’s stories. It’s nice to know you are not alone.”