Upper Gwynedd mother-daughter duo takes on XLH: A legacy of resilience

From the moment she was diagnosed with X-linked hypophosphatemia at just six months old, Ashley Grebe Clemens’s life became a journey of resilience, and now, as a passionate advocate, she fights not only for her own future, but for the future of her young daughter, Sophia, who shares the same rare condition, and others like them.

With Rare Disease Day being Friday, Clemens highlighted XLH, her struggles and current advocacy on social media, and how her daughter – currently Little Miss Lansdale – fights the disorder at eight years old.

“Show your stripes! A very special day that is close to my heart … We have no cure, but we have treatment and it's working for us. We have just loved our community of Xlhers since Sophia got diagnosed right before she turned two and she will be eight in April. We are strong about advocating for everyone with this disease.”

X-linked hypophosphatemia, called XLH, is a rare genetic disorder, primarily affecting bone and mineral metabolism. It affects one in 20,000 people in the United States.

It is caused by mutations in the PHEX gene located on the X chromosome, which leads to a disruption in phosphate regulation in the blood.

“I was diagnosed with XLH when I was six months old. My mother had it,” Clemens told hosts of “Behind the Mystery” on the “The Balancing Act” YouTube channel last year. “I was through childhood physical therapy a lot. In first grade, I started wearing leg braces and used walking devices as I got older.”

Clemens would often attend school in a wheelchair and get special accommodations on school buses.

Her first big surgery was a double osteotomy – surgeons broke both her legs in different spots and pinned bones together to make her legs straighter. She then had to learn how to walk again.

“In my late teens and early 20s, my body was in the best shape. I was not having a lot of symptoms, and I had aged out of pediatric care,” she said. “I didn’t have an adult doctor and I didn’t think I needed it. I had a busy life with work and school, and my body was OK and thriving, and I didn’t feel the need to manage my XLH.”

Then, she began to have constant pain, and by 25, she was walking with crutches or a cane. She could barely walk by the end of the day when out with family.

“My body also started not healing right. I knew something was wrong,” she said.

The PHEX mutation results in phosphate wasting in the kidneys, which lowers phosphate levels in the blood and impairs bone mineralization. Phosphate is critical for bone development, and its deficiency leads to a range of skeletal abnormalities.

XLH is inherited in an X-linked dominant manner, meaning it predominantly affects females, although males can also be affected, typically with more severe symptoms due to having only one X chromosome. If a father has the condition, then only the daughters would get the hereditary, progressive disease, and none of the sons. If a mother has the condition, then she can pass it on to her sons and daughters.

It can also occur spontaneously without any family history, according to Dr. Leanne Ward, professor of pediatrics at the University of Ottawa.

A hallmark of the disease is rickets, a condition characterized by soft, weak bones that are prone to bending and deforming. In addition to skeletal issues, individuals with XLH may also experience dental problems, such as abscesses, tooth loss, and enamel defects.

Symptoms can vary in severity, and some individuals may have milder forms of the disease that only manifest in adulthood.

Features of XLH in adults typically includes bowing of the legs, osteoarthritis, calcification, such as spinal stenosis, short stature, and pain in the bones and joints. Children with XLH often experience delayed walking and disproportionate growth, and they may suffer from fractures or deformities due to weak bones, gait abnormalities and craniosynostotis.

Both adults and children with XLH can have deformities of weight-bearing limbs and a diminished quality of life.

    Ashley Grebe Clemens discusses XLH on "The Balancing Act" on YouTube (Screenshot)  

That last one, however, does not hold true for Ashley and Sophia. 

“Growing up I didn’t know anybody but my biological mother who had XLH,” she said. “It was lonely at points, but my mom didn’t let me sit back and not do things because I couldn’t.”

Being an advocate for the disease and an ambassador has helped her navigate her daughter through the condition.

“I love being a part of the XLH network and being able to interact with different families, telling them never give up and they are not alone,” she said. “Your XLH network is now your family.”

XLH is diagnosed through clinical evaluation, genetic testing, and laboratory analysis. Blood tests typically reveal low phosphate levels, elevated alkaline phosphatase, and normal calcium levels.

Genetic testing can confirm the presence of mutations in the PHEX gene, which is crucial for definitive diagnosis.  

    Characteristics of XLH (Submitted photo)  

Treatment for XLH generally focuses on managing phosphate deficiency and improving bone health. The standard approach includes supplementation with phosphate and active vitamin D, which helps increase phosphate absorption in the intestines and reduces phosphate wasting in the kidneys.

“I’m excited for Sophia’s generation of XLHers,” Clemens said. “They won’t have to go through what we went through as children. I made her a binder with all her milestones, growth charts, medications and symptoms, so when she has to navigate out of pediatrics into adult care, she can take that with her.”

Clemens said the disease does not have to overcome your life.

“The days get better. I tell people, put a smile on your face. That helps,” she said. “There are resources out there with the XLH network. Use them. They’re there to help you.”