Clinical and molecular characterization of Chilean patients with X-linked hypophosphatemia.
Disorders of calcium/phosphate
Osteomalacia and rickets
Pth/Vit D/Fgf23
Journal
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
ISSN: 1433-2965
Titre abrégé: Osteoporos Int
Pays: England
ID NLM: 9100105
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
13
11
2020
accepted:
02
02
2021
pubmed:
6
3
2021
medline:
28
8
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
We report the most comprehensive clinical and molecular characterization of XLH patients performed in Chile. We show high prevalence of musculoskeletal burden and pain, associated with significantly impaired physical capacity and quality of life, with many relevant complications presenting more frequently than previously reported in cohorts from developed countries. Our current understanding of the clinical presentation and natural history of X-linked hypophosphatemia (XLH) comes mainly from cohorts from developed countries, with limited data on the clinical and genetic abnormalities of XLH patients in South America. To describe the clinical, biochemical, and molecular presentation of patients with XLH in Chile. Patients with XLH referred by endocrinologist throughout Chile were included. Demographic data and clinical presentation were obtained from a clinical interview. Surveys were applied for quality of life (QoL), pain, and functionality. FGF23 was measured by ELISA, and genetic testing was performed. Imaging studies were conducted to assess skeletal and renal involvement. We included 26 patients, aged 2-64 years, from 17 unrelated Chilean families. All pediatric patients but only 40% of adults were receiving conventional therapy, while 65% of all patients had elevated alkaline phosphatase. All patients had mutations in PHEX, including 5 novel variants. Radiographic skeletal events (RSE) and enthesopathies in adults were frequent (34% and 85%, respectively). The duration of treatment was associated with fewer RSE (p < 0.05). Most adults reported pain and impaired QoL, and 50% had impaired physical capacity. The number of enthesopathies was associated with worse pain and stiffness scores (p < 0.05). Chilean patients with XLH have a high prevalence of musculoskeletal burden associated with pain and impaired physical capacity and QoL, especially in adults who were generally undertreated. These data identify a significant unmet need, inform our understanding of the current status of patients, and can guide care for XLH patients in similarly socioeconomically defined countries.
Identifiants
pubmed: 33666701
doi: 10.1007/s00198-021-05875-w
pii: 10.1007/s00198-021-05875-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1825-1836Informations de copyright
© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.
Références
Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL (2011) A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res 26:1381–1388
doi: 10.1002/jbmr.340
Florenzano P, Cipriani C, Roszko KL, Fukumoto S, Collins MT, Minisola S, Pepe J (2020) Approach to patients with hypophosphataemia. Lancet Diabetes Endocrinol 8:163–174
doi: 10.1016/S2213-8587(19)30426-7
Marcucci G, Masi L, Ferrarì S, Haffner D, Javaid MK, Kamenický P, Reginster JY, Rizzoli R, Brandi ML (2018) Phosphate wasting disorders in adults. Osteoporos Int 29:2369–2387
doi: 10.1007/s00198-018-4618-2
Carpenter TO (2012) The expanding family of hypophosphatemic syndromes. J Bone Miner Metab 30:1–9
doi: 10.1007/s00774-011-0340-2
Che H, Roux C, Etcheto A, Rothenbuhler A, Kamenicky P, Linglart A, Briot K (2016) Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol 174:325–333
doi: 10.1530/EJE-15-0661
Skrinar A, Dvorak-Ewell M, Evins A, Macica C, Linglart A, Imel EA, Theodore-Oklota C, San Martin J (2019) The lifelong impact of X-linked hypophosphatemia: results from a burden of disease survey. J Endocr Soc 3:1321–1334
doi: 10.1210/js.2018-00365
Mäkitie O, Doria A, Kooh SW, Cole WG, Daneman A, Sochett E (2003) Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 88:3591–3597
doi: 10.1210/jc.2003-030036
Nielsen LH, Rahbek ET, Beck-Nielsen SS, Christesen HT (2014) Treatment of hypophosphataemic rickets in children remains a challenge. Dan Med J 61:A4874
pubmed: 25123121
Friedman NE, Lobaugh B, Drezner MK (1993) Effects of calcitriol and phosphorus therapy on the growth of patients with X-linked hypophosphatemia. J Clin Endocrinol Metab 76:839–844
pubmed: 8473393
Petersen DJ, Boniface AM, Schranck FW, Rupich RC, Whyte MP (1992) X-linked hypophosphatemic rickets: a study (with literature review) of linear growth response to calcitriol and phosphate therapy. J Bone Miner Res 7:583–597
doi: 10.1002/jbmr.5650070602
Colares Neto GP, Pereira RM, Alvarenga JC, Takayama L, Funari MF, Martin RM (2017) Evaluation of bone mineral density and microarchitectural parameters by DXA and HR-pQCT in 37 children and adults with X-linked hypophosphatemic rickets. Osteoporos Int 28:1685–1692
doi: 10.1007/s00198-017-3949-8
Author links open overlay panel, Alonso G, Plantalech L, Guelman R, Gonzalez S, Redal MA, Cassinelli H, Pasqualini T (2011) Familiar hypophosphatemic rickets: molecular findings in thirteen Argentinean families. Bone 48:S288–S289
doi: 10.1016/j.bone.2011.03.744
Connor J, Olear EA, Insogna KL et al (2015) Conventional therapy in adults with X-linked hypophosphatemia: effects on enthesopathy and dental disease. J Clin Endocrinol Metab 100:3625–3632
doi: 10.1210/JC.2015-2199
Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263
pubmed: 951142
doi: 10.1542/peds.58.2.259
Endo I, Fukumoto S, Ozono K et al (2008) Clinical usefulness of measurement of fibroblast growth factor 23 (FGF23) in hypophosphatemic patients: proposal of diagnostic criteria using FGF23 measurement. Bone 42:1235–1239
doi: 10.1016/j.bone.2008.02.014
Holm IA, Nelson AE, Robinson BG, Mason RS, Marsh DJ, Cowell CT, Carpenter TO (2001) Mutational analysis and genotype-phenotype correlation of the PHEX gene in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 86:3889–3899
doi: 10.1210/jcem.86.8.7761
Zhang C, Zhao Z, Sun Y et al (2019) Clinical and genetic analysis in a large Chinese cohort of patients with X-linked hypophosphatemia. Bone 121:212–220
doi: 10.1016/j.bone.2019.01.021
Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502
doi: 10.1136/ard.16.4.494
Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Manaster BJ, Reading JC (2000) Radiographic scoring method for the assessment of the severity of nutritional rickets. J Trop Pediatr 46:132–139
doi: 10.1093/tropej/46.3.132
Thacher TD, Pettifor JM, Tebben PJ, Creo AL, Skrinar A, Mao M, Chen CY, Chang T, San Martin J, Carpenter TO (2019) Rickets severity predicts clinical outcomes in children with X-linked hypophosphatemia: utility of the radiographic Rickets Severity Score. Bone 122:76–81
doi: 10.1016/j.bone.2019.02.010
Boyce AM, Shawker TH, Hill SC, Choyke PL, Hill MC, James R, Yovetich NA, Collins MT, Gafni RI (2013) Ultrasound is superior to computed tomography for assessment of medullary nephrocalcinosis in hypoparathyroidism. J Clin Endocrinol Metab 98:989–994
doi: 10.1210/jc.2012-2747
Osses AR, Yanez VJ, Barria PP, Palacios MS, Dreyse DJ, Diaz PO, Lisboa BC (2010) Reference values for the 6-minutes walking test in healthy subjects 20-80 years old. Rev Med Chil 138:1124–1130
Carpenter TO, Whyte MP, Imel EA et al (2018) Burosumab therapy in children with X-linked hypophosphatemia. N Engl J Med 378:1987–1998
doi: 10.1056/NEJMoa1714641
Gandek B, Ware JE, Aaronson NK et al (1998) Tests of data quality, scaling assumptions, and reliability of the SF-36 in eleven countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol 51:1149–1158
doi: 10.1016/S0895-4356(98)00106-1
Olivares P (2006) Estado de Salud de Beneficiarios del Sistema de Salud de Chile 2004-2005. Superintendencia de Isapres, Departamento de Estudios y Desarrollo
Imel EA, Glorieux FH, Whyte MP et al (2019) Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet 393:2416–2427
doi: 10.1016/S0140-6736(19)30654-3
Seefried L, Smyth M, Keen R, Harvengt P (2020) Burden of disease associated with X-linked hypophosphataemia in adults: a systematic literature review. Osteoporos Int
Verge CF, Lam A, Simpson JM, Cowell CT, Howard NJ, Silink M (1991) Effects of therapy in X-linked hypophosphatemic rickets. N Engl J Med 325:1843–1848
doi: 10.1056/NEJM199112263252604
Goodyer PR, Kronick JB, Jequier S, Reade TM, Scriver CR (1987) Nephrocalcinosis and its relationship to treatment of hereditary rickets. J Pediatr 111:700–704
doi: 10.1016/S0022-3476(87)80245-7
Reusz GS, Hoyer PF, Lucas M, Krohn HP, Ehrich JH, Brodehl J (1990) X linked hypophosphataemia: treatment, height gain, and nephrocalcinosis. Arch Dis Child 65:1125–1128
doi: 10.1136/adc.65.10.1125
Reid IR, Hardy DC, Murphy WA, Teitelbaum SL, Bergfeld MA, Whyte MP (1989) X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults. Medicine (Baltimore) 68:336–352
doi: 10.1097/00005792-198911000-00002
Sullivan W, Carpenter T, Glorieux F, Travers R, Insogna K (1992) A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 75:879–885
pubmed: 1517380
Rasmussen H, Pechet M, Anast C, Mazur A, Gertner J, Broadus AE (1981) Long-term treatment of familial hypophosphatemic rickets with oral phosphate and 1 alpha-hydroxyvitamin D3. J Pediatr 99:16–25
doi: 10.1016/S0022-3476(81)80951-1