X-linked hypophosphataemia

Abstract

X-linked hypophosphataemia is a genetic disease caused by defects in the phosphate regulating endopeptidase homolog X-linked (PHEX) gene and is characterised by X-linked dominant inheritance. The main consequence of PHEX deficiency is increased production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) in osteoblasts and osteocytes. Chronic exposure to circulating FGF23 is responsible for renal phosphate wasting and decreased synthesis of calcitriol, which decreases intestinal phosphate absorption. These mechanisms result in lifelong hypophosphataemia, impaired growth plate and bone matrix mineralisation, and diverse manifestations in affected children and adults, including some debilitating morbidities and possibly increased mortality. Important progress has been made in disease knowledge and management over the past decade; in particular, targeting FGF23 is a therapeutic approach that has substantially improved outcomes. However, patients affected by this complex disease need lifelong care and innovative treatment strategies, such as gene repair of PHEX, are necessary to further limit the disease burden.; Competing Interests: Declaration of interests PK received payment or honoraria for lectures or educational events from Amolyt Pharma, Kyowa Kirin, and Pfizer; received support for attending meetings and travel from Amolyt Pharma, Pfizer, and Recordati; participated on advisory boards of Amolyt Pharma and Ascendis Pharma; and has served as clinical lead of the calcium and bone focus area of the European Society of Endocrinology since 2021. KB received consulting fees from Amgen and Kyowa Kirin; received payment or honoraria for lectures or educational events from Amgen, Kyowa Kirin, and Theramex; and participated on advisory boards of Amgen, Kyowa Kirin, and Theramex. CFM received consulting fees from Alexion and BioMarin; and payment or honoraria for lectures or educational events from BioMarin and Kyowa Kirin. AL received consulting fees from Alexion; received payment or honoraria for lectures or educational events from Kyowa Kirin, Novo Nordisk, and Pfizer; and currently serves as President of the French Society of Pediatrics. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)