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

Orphanet Journal of Rare Diseases

Research

M. Carola Zillikens¹  Dirk Schnabel²  Signe Sparre Beck-Nielsen³  Outi Mӓkitie⁴  Sandro Giannini⁵  M. Zulf Mughal⁶  Dieter Haffner⁷  Elena Levtchenko⁸  Gema Ariceta⁹  Annemieke M. Boot^1,10  Liana Tripto-Shkolnik^1,11  Francesco Emma^1,12  Ola Nilsson^1,13  Maria Luisa Brandi^1,14  Karine Briot^1,15  Angela Williams^1,16  Sue Wood^1,16  Jonathan Liu^1,16  Richard Keen^1,17  Carmen de Lucas Collantes^1,18 

[1] Bone Center, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;Center for Chronically Sick Children, Pediatric Endocrinology, Charité, University Medicine Berlin, Berlin, Germany;Centre for Rare Diseases, Aarhus University Hospital, Åarhus, Denmark;Department of Clinical Medicine, Aarhus University, Åarhus, Denmark;Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;Department of Medicine, Clinica Medica 1, University of Padova, Padua, Italy;Department of Paediatric Endocrinology, Royal Manchester Children’s Hospital, Manchester University Hospital’s NHS Trust, Manchester, UK;Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany;Department of Pediatric Nephrology and Development and Regeneration, University Hospitals Leuven, University of Leuven, Leuven, Belgium;Department of Pediatric Nephrology, Hospital Vall d’Hebron, Universitat Autonoma Barcelona, Barcelona, Spain;Department of Pediatrics, Division of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;Division of Endocrinology, Diabetes and Metabolism, Chaim Sheba Medical Center, Tel Hashomer, Israel;Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;Division of Nephrology, Bambino Gesù Children’s Hospital - IRCCS, Rome, Italy;Division of Pediatric Endocrinology and Center for Molecular Medicine, Department of Women’s and Children’s Health, Karolinska Institutet and University Hospital, Stockholm, Sweden;School of Medical Sciences and Department of Pediatrics, Örebro University and University Hospital, Örebro, Sweden;FIRMO Foundation, Florence, Italy;Donatello Bone Clinic, Florence, Italy;Hôpital Cochin, Service de Rhumatologie, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphate Filière OSCAR, AP-HP, Paris, France;Kyowa Kirin International, Marlow, UK;Royal National Orthopaedic Hospital, Stanmore, UK;Universidad Autónoma de Madrid, Madrid, Spain;Hospital Infantili Niño Jesús, Madrid, Spain;

关键词: X-linked hypophosphatemia (XLH);    Hypophosphatemic rickets;    Rare disease;    International;    Natural history;    Osteomalacia;    Patient registry;    PHEX;    Fibroblast growth factor 23 (FGF23);   

DOI  :  10.1186/s13023-023-02882-4

 received in 2022-12-21, accepted in 2023-08-24,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundX-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.ResultsThe 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 ≥ 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.ConclusionThe 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.

【 授权许可】

CC BY   
© Institut National de la Santé et de la Recherche Médicale (INSERM) 2023

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