Improving the Knowledge of X-linked Hypophosphatemia among Clinicians in the Arabian Gulf and African Countries

Rare bone disorders comprise 5% of all rare disorders.1 These diverse and heterogeneous disorders are often progressive and associatedwith impairedmobility, chronic pain, and poor quality of life. Thus, patients often require lifelong multidisciplinary care, including medical therapies, surgeries, and the provision of aids for activities of daily living. X-linked hypophosphatemia (XLH) is one such rare bone condition. In the current issue of JDEP, Beshyah et al2 undertook an online survey of clinicians in the Middle East and African countries to determine their knowledge of rare metabolic bone disorders and, more specifically, about XLH. While more than 80% of respondents were aware of XLH, the survey identified significant gaps in the clinicians’ knowledge of symptoms of the condition and its management during the life course. The findings of this survey are broadly similar to those reported by Deeb et al.3 They undertook an online survey to determine the awareness, knowledge, and management of XLH among members of the Arab Society for Pediatric Endocrinology and Diabetes. XLH (OMIM 307800) is the most common form of inherited rickets and osteomalacia, affecting 1 in 20,000 to 60,000 people worldwide.4,5 It is caused by mutations in the phosphate-regulating endopeptidase homolog on the X chromosome (PHEX) gene that lead to an increase in fibroblast growth factor 23 (FGF23) levels, which causes renal phosphate wasting, reduced intestinal phosphate absorption, and low active vitamin D, ultimately resulting in chronic hypophosphatemia. It is a progressive disorder that leads to lifelong impairment of skeletal, muscular, dental, and auditory systems.6 It is also associated with poor quality of life in adults5 and increased mortality.7 The burden of the disease in patients with XLH progresses with age.8–10 For more than 40 years, the treatment of XLH consisted of the administration of phosphate salts four to six times a day along with active analogs of vitamin D—calcitriol (1,25 (OH)2D) or alfacalcidol (1-hydroxycholecalciferol). This is often referred to as the “conventional therapy of XLH,”which helps heal rickets and osteomalacia and improve lower limb deformities, linear growth, and dental health.11,12 However, the response to treatment is variable, and many patients are left with residual lower limb deformities requiring surgical correction. The conventional therapy is more effective in children when treatment is started early, ideally<2 years of age.13 Phosphate supplements have an unpleasant taste and side effects: nausea, vomiting, abdominal pains, and diarrhea. Thus, poor adherence to treatment is not uncommon, especially among adolescents. Conventional medicine is also associated with an increased risk of hypercalcemia, nephrocalcinosis, nephrolithiasis, impaired renal function, secondary hyperparathyroidism, and tertiary hyperparathyroidism.11,12 In 2018, burosumab, a fully humanmonoclonal antibody that inhibits excess circulating FGF23, and thus addresses the underlying cause of the disease, was approved for the treatment of XLH in several Gulf Cooperation Council (GCC) countries. Burosumab results in sustained normalization of serum levels of phosphate, 1,25(OH)2D, and alkaline phosphatase. It also results in the healing of rickets and osteomalacia and improves growth rate and myopathy.14