Clinical practice recommendations for the diagnosis and management of X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is caused by mutations in the PHEX gene, which encodes a cell surface bound protein cleavage enzyme predominantly expressed in osteoblasts, osteocytes, and odontoblasts. It is the most common cause of inherited phosphate wasting and associated with severe complications like rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children, as well as hyperparathyroidism, osteomalacia, enthesopathy, osteoarthritis, and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a significant impact on patient outcomes. In this document, the participants have agreed that the diagnosis of XLH is based on signs of rickets/osteomalacia in association with hypophosphatemia, and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of FGF23 level before treatment. Due to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. Here we have summarized the current evidence and provide expert opinions on aspects of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care. Since XLH is a rare disease, the number of available trials is low, and thus the strength of most recommendations is weak - moderate