New Developments in the Treatment of X-Linked Hypophosphataemia: Implications for Clinical Management

Abstract

X-linked hypophosphataemia (XLH) is due to mutations in phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and represents the most common heritable form of rickets. In this condition, the hormone fibroblast growth factor 23 (FGF23) is produced in excessive amounts for still unknown reasons, and causes renal phosphate wasting and suppression of 1,25-dihydroxyvitamin D, leading to low serum phosphate concentrations. Prolonged hypophosphataemia decreases apoptosis of hypertrophic chondrocytes in growth plates (causing rickets) and decreases mineralisation of existing bone (causing osteomalacia). In contrast to historical conventional treatment with oral phosphate supplements and active vitamin D for the last 50 years, the new anti-FGF23 antibody treatment (burosumab) targets the primary pathology by blocking FGF23, thereby restoring phosphate homeostasis. In this review, we describe the changes in treatment monitoring, treatment targets and long-term treatment goals, including future opportunities and challenges in the treatment of XLH in children.

Hypophosphataemic Rickets Secondary to Raine Syndrome: A Review of the Literature and Case Reports of Three Paediatric Patients’ Dental Management

“…Hypophosphataemic rickets is a disorder of the growing skeleton, characterised by hypophosphatemia, impaired intestinal absorption of calcium, and rickets that is resistant to vitamin D [ 11 , 12 ]. Phosphate is the main component of hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ) and essential in cell metabolism (adenosine triphosphate (ATP)) [ 11 ].…”

Dental manifestations of the hypophosphatemic rickets: A case report

“…Ključne reči: hipofosfatemija; rahitis; dentin; periapeksni apsces UVOD Hipofosfatemijski rahitis, takođe poznat kao rahitis rezistentan na vitamin D, ili X-vezani rahitis, nasledni je sindrom koga karakteriše neadekvatna mineralizacija hrskavice i kosti, što dovodi do deformiteta skeleta i poremećaja rasta. Uzrokovan je mutacijom gena PHEX (endopeptidaze odgovorne za regulaciju fosfata šifrovane genom na X hromozomu), dovodeći do porasta fibroblastnog faktora rasta 23 (FGF23), koji je regulator renalne reapsorpcije fosfata [1,2]. Patofiziološki mehanizam se ogleda u smanjenju fosfatne reapsorpcije renalnih tubula, što dovodi do hiperfosfaturije i hipofosfatemije, usled čega se razvija rahitis [3].…”

“…Standardna terapija ovih pacijenata podrazumeva nadoknadu elementarnog fosfora i primenu aktivnih oblika vitamina D [1,3]. U novije vreme pokušava se sa primenom anti-FGF23 antitela koja deluju na primarno oboljenje tako što blokiraju FGF23 i time regulišu homeostazu fosfata [1,2]. Hipofosfatemija je uzrok nastanka displazije dentina zbog poremećaja u mineralizaciji dentinskog matriksa kada se jasno uočava globularni dentin.…”

“…Hypophosphatemic rickets, also known as vitamin D resistant rickets, or X-linked rickets, is an inherited syndrome characterized by inadequate cartilage and bone mineralization leading to skeletal deformities and growth disorders. It is caused by a mutation in the PHEX gene (endopeptidase responsible for the regulation of phosphate encoded by the X chromosome), leading to an increase in fibroblast growth factor 23 (FGF23), which is a regulator of renal phosphate reabsorption [1,2]. The pathophysiological mechanism is reflected in the reduction of phosphate reabsorption by renal tubules, which leads to hyperphosphaturia and hypophosphatemia, causing rickets [3].…”

“…Standard treatment of these patients include the administration of oral phosphate supplements and active vitamin D [1,3]. Recently, attempts have been made to use anti-FGF23 antibodies that act on the primary disease by blocking FGF23 and thus regulating phosphate homeostasis [1,2]. Hypophosphatemia is the cause of dentin dysplasia due to disorders in the mineralization of the dentinal matrix when the globular dentin is clearly observed.…”