The International X-Linked Hypophosphatemia (XLH) Registry: first interim analysis of baseline demographic, genetic and clinical data

• Published in: Orphanet journal of rare diseases 2023-09, Vol.18 (1), p.1-304, Article 304
• Main Authors: Ariceta, Gema, Beck-Nielsen, Signe Sparre, Boot, Annemieke M, Brandi, Maria Luisa, Briot, Karine, de Lucas Collantes, Carmen, Emma, Francesco, Giannini, Sandro, Haffner, Dieter, Keen, Richard, Levtchenko, Elena, MÓkitie, Outi, Mughal, M. Zulf, Nilsson, Ola, Schnabel, Dirk, Tripto-Shkolnik, Liana, Liu, Jonathan, Williams, Angela, Wood, Sue, Zillikens, M. Carola
• Format: Article
• Language: English
• Subjects: Analysis; Arthritis; Body mass index; Care and treatment; Children; Chronic illnesses; Clinical medicine; Consent; Data collection; Data processing; Demographics; Demography; Development and progression; Diagnosis; Family medical history; Fibroblast growth factor 23; Fibroblast growth factor 23 (FGF23); Genetic analysis; Genetic screening; Genetic testing; Hospitals; Hypophosphatemia; Hypophosphatemic rickets; International; Medical research; Medicin och hälsovetenskap; Mutation; Natural history; Osteoarthritis; Osteomalacia; Patient registry; Patients; PHEX mutation; Population; Rare disease; Rare diseases; Registries (in medicine); Regulatory approval; X-linked hypophosphatemia (XLH)
• ISSN: 1750-1172; 1750-1172
• DOI: 10.1186/s13023-023-02882-4

X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive, renal phosphate-wasting disorder characterized by a pathological increase in FGF23 concentration and activity. Due to its rarity, diagnosis may be delayed, which can adversely affect outcomes. As a chronic disease resulting in progressive accumulation of musculoskeletal manifestations, it is important to understand the natural history of XLH over the patient's lifetime and the impact of drug treatments and other interventions. This multicentre, international patient registry (International XLH Registry) was established to address the paucity of these data. Here we present the findings of the first interim analysis of the registry. The International XLH Registry was initiated in August 2017 and includes participants of all ages diagnosed with XLH, regardless of their treatment and management. At the database lock for this first interim analysis (29 March 2021), 579 participants had entered the registry before 30 November 2020 and are included in the analysis (360 children [62.2%], 217 adults [37.5%] and 2 whose ages were not recorded [0.3%]; 64.2% were female). Family history data were available for 319/345 (92.5%) children and 145/187 (77.5%) adults; 62.1% had biological parents affected by XLH. Genetic testing data were available for 341 (94.7%) children and 203 (93.5%) adults; 370/546 (67.8%) had genetic test results; 331/370 (89.5%) had a confirmed PHEX mutation. A notably longer time to diagnosis was observed in adults [greater than or equal to] 50 years of age (mean [median] duration 9.4 [2.0] years) versus all adults (3.7 [0.1] years) and children (1.0 [0.2] years). Participants presented with normal weight, shorter length or height and elevated body mass index (approximately - 2 and + 2 Z-scores, respectively) versus the general population. Clinical histories were collected for 349 participants (239 children and 110 adults). General data trends for prevalence of bone, dental, renal and joint conditions in all participants were aligned with expectations for a typical population of people with XLH. The data collected within the International XLH Registry, the largest XLH registry to date, provide substantial information to address the paucity of natural history data, starting with demographic, family history, genetic testing, diagnosis, auxology and baseline data on clinical presentation.