X‑linked hypophosphataemia (XLH) is a rare, genetic, chronically debilitating and deforming condition. It is an X‑linked dominant disorder caused by mutations in the PHEX gene that inactivate the PHEX enzyme. This leads to errors in phosphate sensing and increased levels of fibroblast growth factor 23 (FGF23). Excess FGF23 causes impaired phosphate conservation and excessive phosphate excretion. It also supresses vitamin D production, which causes reduced calcium and phosphate absorption.
Because XLH is a genetic condition, it often affects several members of a family. Skeletal abnormalities such as bowed or bent legs, below average height and irregular growth of the skull are early signs of XLH. Children may also present with delayed walking or waddling gait. Bone defects are common in children with XLH, and can cause pain and subsequently limit physical functioning. When bone growth stops, bone deformities become irreversible and can be the source of continuing pain. Other manifestations of XLH include dental problems and hearing loss. Adults with XLH can have symptoms such as osteomalacia (softening of the bones, which causes an increased risk of stress fractures and other complications), muscle weakness, pain and fatigue.
The aim of current treatment is to improve growth, decrease morbidity, prevent skeletal deformities and reduce pain. For most people with XLH, clinical management consists of vitamin D supplementation and oral phosphate (often with dosing 4 to 6 times a day). People with XLH often need orthopaedic surgery to correct bone deformities.