Fahad Al Juraibah1,2, Elham Al Amiri3, Mohammed Al Dubayee1,2, Jamal Al Jubeh4, Hessa Al Kandari5,6, Afaf Al Sagheir7, Adnan Al Shaikh8, Salem A Beshyah9,10, Asma Deeb11, Abdelhadi Habeb2,12, Manal Mustafa13, Hanaa Zidan14, M Zulf Mughal15,16. 1. Department of Paediatrics, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia. 2. College of Medicine, King Saud bin Abdulaziz University for Health Science, Riyadh, Saudi Arabia. 3. Al Qassimi Women & Children Hospital, Sharjah, United Arab Emirates. 4. Division of Paediatric Endocrinology, Institute of Paediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates. 5. Farwaniya Hospital, Kuwait City, Kuwait. 6. Department of Population Health, Dasman Diabetes Institute, Kuwait City, Kuwait. 7. King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia. 8. King Abdulaziz Medical City, Ministry of the National Guard, Jeddah, Saudi Arabia. 9. Diabetes and Endocrine Clinic, Mediclinic Airport Road, Abu Dhabi, United Arab Emirates. 10. Department of Medicine, Dubai Medical College for Girls, Dubai, United Arab Emirates. 11. Division of Paediatric Endocrinology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates. 12. Department of Paediatrics, Prince Mohammed bin Abdulaziz Hospital for National Guard, Al-Madinah, Saudi Arabia. 13. Latifa Women & Children Hospital, Dubai Health Authority, Dubai, United Arab Emirates. 14. American Hospital, Dubai, United Arab Emirates. 15. Royal Manchester Children's Hospital, Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK. zulf.mughal@mft.nhs.uk. 16. Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK. zulf.mughal@mft.nhs.uk.
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.
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.
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