Enrique Rodríguez-Rubio1, Helena Gil-Peña2, Sara Chocron3, Leire Madariaga4, Francisco de la Cerda-Ojeda5, Marta Fernández-Fernández6, Carmen de Lucas-Collantes7, Marta Gil8, María Isabel Luis-Yanes9, Inés Vergara10, Juan David González-Rodríguez11, Susana Ferrando12, Montserrat Antón-Gamero13, Marta Carrasco Hidalgo-Barquero14, Angustias Fernández-Escribano15, Mº Ángeles Fernández-Maseda16, Laura Espinosa17, Aniana Oliet18, Antonio Vicente19, Gema Ariceta3, Fernando Santos20,2. 1. Pediatric Research, Medicine Department, University of Oviedo, Oviedo, Spain. erodrr00@gmail.com. 2. AGC Pediatría, Hospital Universitario Central de Asturias, Oviedo, Spain. 3. Servicio de Nefrología Pediátrica, Hospital Vall D'Hebron, Universitat Autónoma de Barcelona, Barcelona, Spain. 4. Servicio Nefrología Pediátrica, IIS Biocruces-Bizkaia, Universidad del País Vasco UPV/EHU, Hospital Universitario Cruces, Barakaldo, Spain. 5. Unidad de Nefrología Pediátrica, Hospital Virgen del Rocío, Sevilla, Spain. 6. Servicio Pediatría, Complejo Asistencial Universitario de León, León, Spain. 7. Servicio Nefrología, Hospital Niño Jesús, Madrid, Spain. 8. Servicio Pediatría, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 9. Servicio Pediatría, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain. 10. Servicio Pediatría, Complexo Hospitalario Universitario A Coruña (CHUAC), A Coruña, Spain. 11. Unidad de Nefrología, Hospital General Universitario Santa Lucia, Cartagena, Spain. 12. Servicio de Pediatría, Hospital Clínico Universitario de Valencia, Valencia, Spain. 13. Unidad Nefrología Pediátrica, Hospital Universitario Reina Sofia, Córdoba, Spain. 14. Unidad de Nefrología Pediátrica, Hospital Universitario de Badajoz, Badajoz, Spain. 15. ServicioNefrología Infantil, Hospital Infantil Gregorio Marañón, Madrid, Spain. 16. Unidad de Nefrología Pediátrica, Hospital Virgen de la Salud, Toledo, Spain. 17. Servicio Nefrología infantile, Hospital Universitario Infantil La Paz, Madrid, Spain. 18. Servicio Nefrología, Hospital Severo Ochoa, Leganés, Spain. 19. Servicio Pediatría, Hospital Vega Baja, Orihuela, Spain. 20. Pediatric Research, Medicine Department, University of Oviedo, Oviedo, Spain.
Abstract
BACKGROUND: X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. RESULTS: The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was - 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below-2. All cases had hypophosphatemia, serum phosphate being - 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype-phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. CONCLUSIONS: This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.
BACKGROUND:X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. RESULTS: The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was - 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below-2. All cases had hypophosphatemia, serum phosphate being - 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype-phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patientsnephrocalcinosis. CONCLUSIONS: This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.
Entities:
Keywords:
Bone deformities; Growth retardation; Inherited hypophosphatemia; Rickets; XLH
Authors: R Fuente; H Gil-Peña; D Claramunt-Taberner; O Hernández; A Fernández-Iglesias; L Alonso-Durán; E Rodríguez-Rubio; F Santos Journal: Rev Endocr Metab Disord Date: 2017-03 Impact factor: 6.514
Authors: Enrique Rodríguez-Rubio; Helena Gil-Peña; Sara Chocron; Leire Madariaga; Francisco de la Cerda-Ojeda; Marta Fernández-Fernández; Carmen de Lucas-Collantes; Marta Gil; María Isabel Luis-Yanes; Inés Vergara; Juan David González-Rodríguez; Susana Ferrando; Montserrat Antón-Gamero; Marta Carrasco Hidalgo-Barquero; Angustias Fernández-Escribano; Mº Ángeles Fernández-Maseda; Laura Espinosa; Aniana Oliet; Antonio Vicente; Gema Ariceta; Fernando Santos Journal: Orphanet J Rare Dis Date: 2021-04-01 Impact factor: 4.123
Authors: Soodabeh Sarafrazi; Sean C Daugherty; Nicole Miller; Patrick Boada; Thomas O Carpenter; Lauren Chunn; Kariena Dill; Michael J Econs; Scott Eisenbeis; Erik A Imel; Britt Johnson; Mark J Kiel; Stan Krolczyk; Prameela Ramesan; Rebecca Truty; Yves Sabbagh Journal: Hum Mutat Date: 2021-12-05 Impact factor: 4.700
Authors: M I Luis Yanes; M Diaz-Curiel; P Peris; C Vicente; S Marin; M Ramon-Krauel; J Hernandez; J J Broseta; L Espinosa; S Mendizabal; L Perez-Sukia; V Martínez; C Palazón; J A Piñero; M A Calleja; J Espin; R Arborio-Pinel; G Ariceta Journal: Orphanet J Rare Dis Date: 2022-07-29 Impact factor: 4.303
Authors: Rocío Fuente; María García-Bengoa; Ángela Fernández-Iglesias; Helena Gil-Peña; Fernando Santos; José Manuel López Journal: Int J Mol Sci Date: 2022-01-15 Impact factor: 5.923