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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.

We suggest that patUPD20 should be considered in the evaluation of patients with sporadic PHP1b.

Rickets is disorder of a growing child arising from disorders that result in impaired apoptosis of hypertrophic cells and mineralization of the growth plate. Rickets due to nutritional causes remains an important global problem. The factors responsible for resurgence of rickets among dark-skinned infants living in developed countries include the following: residence in northern or southern latitudes, voluntary avoidance of exposure to solar ultraviolet B radiation, maternal vitamin D deficiency during pregnancy, and prolonged breastfeeding without provision of vitamin D supplements. Fibroblast growth factor 23 (FGF23), secreted by osteocytes, is an important regulator of serum phosphate and 1,25(OH)(2)D(3) levels. Hypophosphatemic rickets resulting from increased synthesis or under-catabolism of FGF23 is reviewed.