Abstract
BackgroundX-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in fibroblast growth factor (FGF) 23 concentration and activity; XLH has an incidence of approximately 1 in 20–25,000 individuals. Excess FGF23 activity leads to increased phosphate excretion in the kidneys – mediated by downregulation of renal tubular phosphate transporters – and reduced phosphate absorption in the intestines – due to impaired vitamin D activation. This results in impaired bone growth and mineralisation, short and disproportionate stature, leg bowing, musculoskeletal pain, spontaneous dental abscesses, rickets, and osteomalacia. The spectrum of manifestations differs between paediatric and adult patients. Those involved in the treatment of this condition face many challenges, including a lack of robust natural history and demographic data. This multicentre, international, rare-disease patient registry (XLH Registry) was established to address the paucity of data in XLH and to help inform future clinical practice.ResultsThe XLH Registry collects standard diagnostic and monitoring practice data, including (where applicable) diagnosis and disease progression history, treatment regimens and family history; the protocol does not mandate any interventions or clinical assessments. The XLH Registry aims to recruit 1200 paediatric and adult patients with XLH over 10 years, and several data analyses and peer-reviewed publications are expected to be generated throughout this period. A post-authorisation safety study for Bburosumab, for which the registry Sponsor is the marketing authorisation holder, will be nested as a sub-study within the XLH Registry via a subsequent protocol amendment.ConclusionThe data collected within this rare-disease patient registry will be utilised to synthesise real-world evidence to inform the management of XLH, to improve the quality of life and standard of care of patients living with this rare debilitating disease.
Highlights
X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in the serum concentrations and activity of fibroblast growth factor (FGF) 23
Study population To be eligible for inclusion in the XLH Registry, patients must meet all of the following criteria: 1. Male or female subjects of all ages at baseline
Within the field of rare diseases, patient registries can be an invaluable source of natural history and epidemiological, clinical and medical information which may otherwise be unobtainable by traditional means [28]
Summary
X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in the serum concentrations and activity of fibroblast growth factor (FGF) 23. Increased FGF23 activity is responsible for downregulation of the sodium-dependent phosphate co-transporters NPT2a and NPT2c in the proximal renal tubules, alongside diminished synthesis and increased catabolism of active vitamin D due to decreased 1α-hydroxylase and increased 24-hydroxylase enzyme activity The combination of these physiological changes results in increased phosphate wasting via the kidneys and reduced phosphate absorption in the intestines; these impairments in phosphate homeostasis lead to chronic hypophosphataemia [1]. X-linked hypophosphataemia (XLH) is a rare, hereditary, progressive and lifelong phosphate wasting disorder characterised by pathological elevations in fibroblast growth factor (FGF) 23 concentration and activity; XLH has an incidence of approximately 1 in 20–25,000 individuals.
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