People with X-linked hypophosphatemia (XLH) frequently experience pain, stiffness, and fatigue, which have a significant impact on their physical functioning, mental health, and daily lives, a study reports.
They also experience worsening of symptoms over time, making them concerned about the future and worried about having children with XLH, the researchers said.
The study, “Exploring the burden of X-linked hypophosphatemia: a European multi-country qualitative study,” was published in Quality of Life Research.
XLH is caused by mutations in the PHEX gene, which codes for the PHEX enzyme. These mutations lead to excessive activity of the fibroblast growth factor 23 (FGF23) — crucial for bone strength — which in turn increases the excretion of phosphate from the body and decreases its levels in the blood.
Phosphate is important for many cellular processes, including the development and growth of bones and teeth. As XLH is a chronic disease, patients often experience lifelong and progressive bone and joint damage, dental issues, and reduced mobility.
For the past few decades, treatment consisted of conventional therapy with oral phosphate supplementation and active vitamin D, but incomplete healing of rickets and short stature may still have occurred. Few studies on health-related quality of life (HRQoL) in XLH have been published to date, and factors such as the emotional and psychosocial impact of living with XLH have not been explored.
In the study, researchers in the U.K. set out to investigate the XLH patient experience of pain, stiffness, and fatigue as well as the impact of these symptoms on their physical, psychological, and social well-being.
The study included 30 adults with XLH (26 or older) living in Finland, France, Germany, Luxembourg, and the U.K. between January and April 2019. They were recruited through patient associations and interviewed via telephone. To be included, patients could not have received treatment with Crysvita (burosumab) to ensure that the study captured only the experience of patients on conventional therapy. Kyowa Kirin, marketer of Crysvita, funded the study.
Pain, stiffness, fatigue, and mobility issues were the most common symptoms that patients reported as affecting their daily lives. Unlike pain and stiffness, many patients were not sure if fatigue was also experienced by healthy people or if it could be caused by their disease.
Over three quarters of the participants reported dental issues and short stature. Most participants also reported bone deformities, although some problems had been corrected through surgery.
“Participants often expressed ambivalence towards the effectiveness of conventional XLH treatment due to a perceived lack of or limited impact on XLH symptoms,” the researchers wrote.
Patients commonly reported difficulty standing and walking, and walking slower, and also the significant impact this had on their ability to do housework (such as grocery shopping or cooking), caregiving, and overall any social or work-related activity that required walking or standing for long periods of time.
Negative social experiences were common. These included being bullied, stared at, or made to feel self-conscious about their physical appearance, which led to lower self-esteem and going out less often.
“Nevertheless, it was also common for participants to report having developed mental resilience as a consequence of XLH which they perceived as a positive impact and helped them cope with their condition,” the researchers said.
In terms of their experience with pain, many patients reported experiencing pain since childhood, while others reported its onset in adulthood. Those who reported a change in their pain experience over time usually said it had worsened, while a few said they experienced reduced pain following surgery. The most frequently described pain trigger was movement. Other triggers included specific postures, changes in weather, humidity, or being stationary.
Most patients used analgesics, ranging from over-the-counter painkillers to steroid injections and morphine. Patients had varied responses to these treatments, but most said that they did not achieve complete relief. Some people used anti-depressants and conventional XLH treatment to lessen pain, while others used methods such as hot baths, exercise and stretching, physiotherapy, massage, and alternative therapies such as acupuncture.
As a lifelong disease, XLH had a significant psychosocial impact on patients. Some expressed worries about the future, namely about disease progression, symptom worsening, inability to work, worry about their children with XLH, and side effects of medication.
“A few also reported observing their elderly parents’ condition worsening over time which caused concern for their own future,” the researchers wrote.
Some participants considered the risk of passing the XLH-causing gene mutation to their children, while others “did not mention going through a deliberate decision-making process,” the study stated. Among those expressing concern, some decided not to have children or delayed having them, and others considered options such as adoption or donor eggs.
Though guilt for passing down the condition was commonly reported, “a few participants stated that XLH had not affected their decision to have children because they believed the condition could be managed well,” the researchers wrote.
In addition, clinical trials with XLH patients have typically used assessment tools developed for more common musculoskeletal or unrelated conditions to measure pain, stiffness, and fatigue.
“The present study results confirm the importance and impact of these symptoms on everyday life in XLH and therefore highlight the importance of measuring these symptoms in XLH trials,” the researchers said.
We are sorry that this post was not useful for you!
Let us improve this post!
Tell us how we can improve this post?