Leukodystrophies are a group of conditions that affect the white matter of the brain, or the myelin sheath, which surrounds and protects the nerve cells in the brain and spinal cord and assists with transmission of messages between cells. One type of leukodystrophy is called 4H leukodystrophy or POL 3-related leukodystrophy. 

This rare genetic disorder is characterized by a deficiency in myelination (hypomyelination), differences in hormone production (hypogonadotropic hypogonadism) and abnormal development of teeth (hypodontia). Symptoms of 4H leukodystrophy can include problems with balance, walking and muscle coordination, stiff limbs and limited fine motor development, learning disabilities, delayed or atypical puberty, abnormal tooth development, and vision and speech problems. Children typically start to show symptoms in early infancy or as toddlers.

Weston was 18 months old when his parents — Gabe and Ashley — noticed issues with the way his teeth were growing in, instability when he walked, and abnormal breathing episodes when he slept. They didn’t realize all these things were related and signs of 4H leukodystrophy. Neither did their pediatrician or neurologist.

It took many doctor visits and diagnostic tests before a genetic test came back positive for the condition when Weston was 3 years old. Their local neurologist was honest: He knew nothing about 4H leukodystrophy. So, he referred the family to the experts at Children’s Hospital of Philadelphia’s Leukodystrophy Center of Excellence.

Support from CHOP’s Leukodystrophy Center team

The family flew out to Philadelphia to meet with the multidisciplinary team in the Leukodystrophy Center. The team at Children’s Hospital of Philadelphia (CHOP) explained the condition in detail, answered the family’s questions, and gave them recommendations on how to manage Weston’s care back home. They encouraged Gabe and Ashley to enroll Weston in as many rehabilitation therapies — physical therapy (PT), speech therapy and occupational therapy (OT) — as they could. They also recommended braces to support his ankles.

Right now, there is no targeted therapy or cure for 4H leukodystrophy. Children need regular monitoring and support from a range of medical specialists and therapists to manage symptoms and maximize their quality of life.

“The condition is progressive, so eventually he will lose certain functions like his ability to walk and eat on his own,” says Ashley. “But every case looks different, and there’s no timeline on when that will happen.”

The hope is that someday soon — before Weston and other kids like him lose too much function — a gene therapy that can slow down the progression of the disease will be available. The team at CHOP not only has its finger on the pulse of the latest treatments available, but also is leading the search for new therapeutic options.

Participating in pivotal research 

In October 2023, CHOP and the Yaya Foundation for 4H Leukodystrophy co-hosted a family and scientific conference centered around 4H leukodystrophy. Both groups are dedicated to furthering research efforts and providing education, support and advocacy for children and families living with the condition.

The Leukodystrophy Center hosts one of the world’s largest leukodystrophy-specific data and sample repositories — formally known as the Myelin Disorders Biorepository Project (MDBP) — that has supported key leukodystrophy discoveries over the past two decades. It continues to serve as an essential resource for patients and families, clinicians, and research collaborators.

Five-year-old Weston and his family flew from their home in Boise, Idaho to Philadelphia to be at the conference. It was the first time the family had returned to CHOP since Weston’s diagnosis.

The conference, attended by more than 100 people, was a rare chance to meet other families affected by the condition, learn about promising research, access resources to improve day-to-day life, and get guidance from experts on how best to manage the condition. The family also took advantage of the opportunity for Weston to undergo a clinical evaluation with the Leukodystrophy Center team and participate in PT, OT, and neuropsychiatric evaluations as well as a blood sample collection for research studies.

Staying hopeful for advances on the horizon

Weston is a sweet, active boy who likes superheroes and Legos, likes to play on the playset and trampoline in his backyard, and loves music and fishing. The family is devastated that his diagnosis may limit his lifespan, but they try to focus on the positives and stay hopeful for advances on the horizon.

"We have hard days, and we have good days,” says Ashley. “It took over a year for me to accept it because it’s life-shortening, and no parent wants to hear that. But he’s happy and he’s healthy — other than the 4H leukodystrophy — so we’re really lucky.”