Diagnosis and management of X-linked hypophosphatemia in children and adolescent in the Gulf Cooperation Council countries

Abstract

Introduction X-linked hypophosphatemia (XLH) is a rare inherited cause of hypophosphatemic rickets and osteomalacia. It is caused by mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX). This results in increased plasma fibroblast growth factor-23 (FGF23), which leads to loss of renal sodium-phosphate co-transporter expression leading to chronic renal phosphate excretion. It also leads to low serum 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in impaired intestinal phosphate absorption. Chronic hypophosphatemia in XLH leads to impaired endochondral mineralization of the growth plates of long bones with bony deformities. XLH in children and adolescents also causes impaired growth, myopathy, bone pain, and dental abscesses. XLH is the most frequent inherited cause of phosphopenic rickets/osteomalacia. Hypophosphatemia is also found in calcipenic rickets/osteomalacia as a result of secondary hyperparathyroidism. Thus, chronic hypophosphatemia is a common etiologic factor in all types of rickets. Results There is considerable overlap between symptoms and signs of phosphopenic and calcipenic rickets/osteomalacia. Wrong diagnosis leads to inappropriate treatment of rickets/osteomalacia. Nutritional rickets and osteomalacia are common in the Gulf Cooperation Council countries which include Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman. Due to high levels of consanguinity in the region, genetic causes of phosphopenic and calcipenic rickets/osteomalacia are also common. Conclusion This guideline was developed to provide an approach to the diagnosis of XLH, especially where there is no family history of the disease, and that other related conditions are not mistaken for XLH. We also guide the medical management of XLH with conventional treatment and with burosumab, a recombinant human IgG1 monoclonal antibody to FGF23.

Doctors' Perceptions of Rare Bone Disorders and X-Linked Hypophosphatemia: A Survey from Africa and the Middle East

“…30 Burosumab is now a standard approach in all guidelines and expert opinions. 9 10 11 12 A minority of respondents in the present study had patients with XLH in their clinics. Nonetheless, it is reassuring that most of them included suspected hypophosphatemic rickets as the likely diagnosis in the survey's case scenario, although many considered osteogenesis imperfecta at the top of their differential diagnosis.…”

“…8 Perhaps due to its rarity, XLH is poorly known, and diagnosis may frequently be delayed despite the availability of comprehensive national, regional, and international guidelines. 9 10 11 Conventional treatment has been based on oral phosphate salt supplementation and activated vitamin D analogs which cannot cure the disease. Over the past decade, several advanced treatment options have been introduced and shown to be effective for many metabolic bone disorders, such as Burosumab for XLH.…”

A Case of X-Linked Hypophosphatemic Rickets with Dentin Dysplasia in Mandibular Third Molars

“…XLH is a rare genetic disorder caused by mutation of PHEX [ 4 , 5 , 21 ]. Because PHEX is located on the X chromosome, random inactivation of the X chromosome in females is predicted to result in a milder phenotype than in males with complete loss of PHEX [ 10 , 22 , 23 ].…”

“…The prevalence of XLH is estimated to be 1/20,000 people in North America and Japan, and no substantial race-related difference in the incidence of XLH has been identified [ 2 ]. XLH is caused by mutation of the PHEX gene (phosphate-regulating gene with homology to endopeptidases on the X chromosome) [ 4 , 5 ]. XLH is known to cause the following systemic symptoms due to inhibition of phosphorus reabsorption by PHEX : severe deformities of the lower extremities such as O- and X-legs, growth disturbances such as short stature, bone and muscle pain, and decreased quality of life [ 4 , 5 ].…”

“…XLH is caused by mutation of the PHEX gene (phosphate-regulating gene with homology to endopeptidases on the X chromosome) [ 4 , 5 ]. XLH is known to cause the following systemic symptoms due to inhibition of phosphorus reabsorption by PHEX : severe deformities of the lower extremities such as O- and X-legs, growth disturbances such as short stature, bone and muscle pain, and decreased quality of life [ 4 , 5 ]. Because XLH is a multisystem disease, it requires a multidisciplinary approach in specialized fields [ 4 , 5 ].…”