The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey

Abstract

Context X-linked hypophosphatemia (XLH) is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal abnormalities, and growth impairment. We aimed to understand the burden of disease of XLH across the lifespan. Methods Responses were collected from adults with XLH and parents/caregivers of a child with XLH in an online survey, including multiple-choice and open-ended questions on demographics, disease manifestations, treatment history, assistive device use, and age-specific patient-reported outcomes (PROs). Results Data were collected from 232 adults with XLH (mean age, 45.6 years; 76% female) and 90 parents/caregivers of a child with XLH (mean age, 9.1 years; 56% female). Mean age recalled for symptom onset was 3.2 years for adults and 1.3 years for children. When surveyed, nearly all children (99%) and 64% of adults were receiving oral phosphate, active vitamin D, or both. Prior participation in a trial investigating burosumab, a fully human monoclonal antibody against FGF23, was reported in 3% of children and 10% of adults; of these respondents, only one child reported current treatment with burosumab at the time of the survey. Both children and adults reported typical features of XLH, including abnormal gait (84% and 86%, respectively), bowing of the tibia/fibula (72% and 77%), and short stature (80% and 86%). Nearly all adults (97%) and children (80%) reported bone or joint pain/stiffness. Adults reported a history of fractures (n/N = 102/232; 44%), with a mean (SD) age at first fracture of 26 (16) years. Adults reported osteophytes (46%), enthesopathy (27%), and spinal stenosis (19%). Mean scores for PROs evaluating pain, stiffness, and physical function were worse than population norms. Analgesics were taken at least once a week by 67% of adults. Conclusions Despite the common use of oral phosphate and active vitamin D established in the 1980s, children with XLH demonstrate a substantial disease burden, including pain and impaired physical functioning that persists, as demonstrated by similar responses reported in adults with XLH.

Exploring the burden of X-linked hypophosphatemia: a European multi-country qualitative study

“…The evidence suggests that the XLH HRQoL is comparable with other rare musculoskeletal diseases such as osteogenesis imperfecta and fibrous dysplasia and higher than that of similar, but more common musculoskeletal disorders such as axial spondyloarthritis [4,9]. Relatedly, a recent survey among adults with XLH showed low satisfaction with HRQoL and average physical function scores of more than one standard deviation below the population norm [10].…”

Positive Response to One-Year Treatment With Burosumab in Pediatric Patients With X-Linked Hypophosphatemia

“…Classical medical treatment of XLH is based on the oral administration of phosphate supplements and 1-hydroxy metabolites of vitamin D, given chronically, at least until the end of body growth (4). This therapy usually heals the active radiological lesions of rickets and improves growth but does not normalize serum phosphate, does not avoid major clinical manifestations of the disease, does not result in the achievement of a normal final adult height and entails the risk of potential undesirable side effects such as nephrocalcinosis or hyperparathyroidism (5,6).…”

Health-related quality of life in children and adults with X-linked hypophoshatemia

“…Thus, HRQoL in adults is reduced by complications such as deformities, pseudofractures, bone and joint pain, and stiffness of lower extremities [19]. However, many XLH complications in adult patients are thought to be consequences of suboptimal disease management during childhood, as well as inadequate transition to adult health care [8,20,21].…”