Characterization of otologic involvement in patients with X‐Linked Hypophosphatemia

Abstract

X-linked hypophosphatemia (XLH) is the most common form of hereditary hypophosphatemic rickets and is characterised by an increased production of the hormone fibroblast growth factor 23 (FGF23), caused by mutations in the PHEX gene. The excess of FGF23 determines a decrease in the renal tubular reabsorption of phosphate and inhibits 1-alpha-hydroxylase, which decreases the synthesis of 1,25-dihydroxycholecalciferol (1,25(OH) 2 D) and therefore diminishes intestinal phosphate absorption. Both mechanisms contribute to chronic hypophosphatemia. 1 Chronic hypophosphatemia causes impaired skeletal mineralization, which often results in stunted linear growth, lower limb deformity, pain and physical dysfunction. Other manifestations involve spontaneous dental abscesses, enthesopathies, osteoarthritis and muscle weakness. Conventional treatment includes oral phosphate and active vitamin D supplementation. In children, it has demonstrated improvement of bone deformity and height outcome.However, efficacy of conventional treatment in adults remains controversial. 1,2 Hearing loss has been associated with XLH, with a wide range of prevalence, ranging from 16% to 76%, depending on the studied population, age and diagnostic criteria, with a wide range of clinical presentation. [3][4][5][6] Little is known about the otorhinolaryngological presentation of XLH in cohorts from developing countries. The aim of this study was to describe these manifestations in XLH patients from our region and to explore its association with the severity of biochemical and skeletal involvement. | ME THODS | Study designA cross-sectional observational study was performed. Diagnosis of XLH was based on clinical, radiological and biochemical findings that indicated congenital hypophosphatemia due to isolated renal phosphate wasting, confirmed with genetic analysis with PHEX mutation. Patients were recruited between May and

Anticipated effects of burosumab treatment on long-term clinical sequelae in XLH: expert perspectives

“…Hearing loss and tinnitus are other known clinical consequences of XLH ( 19 , 20 , 43 , 45 ), which can reduce health-related quality of life ( 46 ). It is hypothesized that hypophosphatemia and osteomalacia associated with increased FGF23 in XLH can lead to temporal bone malformation.…”

“…Chronic hypophosphatemia and osteomalacia combined with the irreversible skeletal deformities acquired in childhood are linked to progressive clinical sequelae in adulthood, including osteoarthritis, enthesopathies, osteomalacic fractures, and spinal stenosis (10, 12), with the prevalence and severity of many increasing with age (8,(13)(14)(15). Given the multisystem impact of XLH, it is unsurprising that adults with XLH suffer from considerable chronic pain, impaired mobility, loss of physical function and hearing, and decreased health-related quality of life (16)(17)(18)(19)(20).…”