ESPE Abstracts (2018) 89 S7.1

X-linked Hypophosphataemic Rickets: Disease and Treatment

Agnes Linglart


APHP, Paris, France


XLH is a dominant disorder with a prevalence of approximately 1.7/100,000 children to 4.8/100,000 persons. PHEX, the gene responsible for XLH was identified on chromosome Xp22. It codes for a cell surface-bound protein-cleaving enzyme expressed predominantly in bone and teeth. The altered function of PHEX causes both the mineralization defect and the renal phenotypic abnormalities of XLH. Clinical manifestations of XLH occur most often around the age of walking, despite an adequate vitamin D supplementation. In children the primary clinical symptoms are skeletal pain and deformity, abnormal gait, decreased growth velocity, dental abscesses and craniosynostosis. In adults, osteomalacia, bone pain, stiffness and enthesopathy are typical findings. Dizziness and deafness due to abnormalities of the inner ear may develop towards adulthood. Many patients may have partial synostosis of the sagittal sutures leading to a dolichocephalic shape of the head. This, however, is rarely accompanied by intracranial hypertension. XLH is characterized by elevated ALP, low serum phosphate, phosphate wasting and elevated levels of circulating FGF23. On radiographs, the metaphyseal signs are those of common rickets. In contrast, the bone has a mesh-like appearance with gross bone trabeculations and the cortices are thick. The current conventional treatment of XLH associates vitamin D analogues and repeated doses of phosphate supplements. Active vitamin D analogues are given to counter calcitriol deficiency, prevent secondary hyperparathyroidism, and increase phosphate absorption from the gut. The optimal dose of treatment varies from patient to patient. Higher doses are given during period of rapid growth and at initiation of treatment when the skeleton requires mineral accretion. Thereafter, doses need to be adjusted according to the efficacy, i.e. improvement of bone deformities, rickets on radiographs and ALP, and safety, i.e. prevention of nephrocalcinosis and hyperparathyroidism. The human anti-FGF23 monoclonal antibody, burosumab, is now an alternative to the conventional therapy as it was approved by The FDA for adults and children and by the EMA in children, and is now available in some countries. We do not have enough evidence yet to compare both therapeutic strategies and we do not know if one has better short/mid/long term results than the other. The administration of growth hormone improves growth in prepubertal children with XLH but no clear indication exist to support systematic treatment of patients with XLH. Surgery is indicated for severe bowing or tibial torsion unlikely to improve with medical management alone.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts