Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia

  • Olaya Hernández-Frías
  • Helena Gil-Peña
  • José M. Pérez-Roldán
  • Susana González-Sanchez
  • Gema Ariceta
  • Sara Chocrón
  • Reyner Loza
  • Francisco de la Cerda Ojeda
  • Leire Madariaga
  • Inés Vergara
  • Marta Fernández-Fernández
  • Susana Ferrando-Monleón
  • Montserrat Antón-Gamero
  • Ángeles Fernández-Maseda
  • M. Isabel Luis-Yanes
  • Fernando SantosEmail author
Original Article



To find out if cardiovascular alterations are present in pediatric patients with X-linked hypophosphatemia (XLH).

Study design

Multicentre prospective clinical study on pediatric patients included in the RenalTube database ( with genetically confirmed diagnosis of XLH by mutations in the PHEX gene. The study’s protocol consisted of biochemical work-up, 24-h ambulatory blood pressure monitoring (ABPM), carotid ultrasonography, and echocardiogram. All patients were on chronic treatment with phosphate supplements and 1-hydroxy vitamin D metabolites.


Twenty-four patients (17 females, from 1 to 17 years of age) were studied. Serum concentrations (X ± SD) of phosphate and intact parathyroid hormone were 2.66 ± 0.60 mg/dl and 58.3 ± 26.8 pg/ml, respectively. Serum fibroblast growth factor 23 (FGF23) concentration was 278.18 ± 294.45 pg/ml (normal < 60 pg/ml). Abnormally high carotid intima media thickness was found in one patient, who was obese and hypertensive as revealed by ABPM, which disclosed arterial hypertension in two other patients. Z scores for echocardiographic interventricular septum end diastole and left ventricular posterior wall end diastole were + 0.77 ± 0.77 and + 0.94 ± 0.86, respectively. Left ventricular mass index (LVMI) was 44.93 ± 19.18 g/m2.7, and four patients, in addition to the obese one, had values greater than 51 g/m2.7, indicative of left ventricular hypertrophy. There was no correlation between these echocardiographic parameters and serum FGF23 concentrations.


XLH pediatric patients receiving conventional treatment have echocardiographic measurements of ventricular mass within normal reference values, but above the mean, and 18% have LVMI suggestive of left ventricular hypertrophy without correlation with serum FGF23 concentrations. This might indicate an increased risk of cardiovascular involvement in XLH.


XLH FGF23 Left ventricular hypertrophy PHEX gene Intima-media of carotid artery 



Serum FGF23 determinations were performed in Dr. Mariano Rodríguez’s laboratory (IMIBIC/Hospital Universitario Reina Sofía, Córdoba, Spain), partly funded by the Funfación Nutrición y Crecimiento.


This study was funded by grants PI12/00987 (National Plan I + D + I 2008–2011) and PI15/02122 (National Plan I + D + I 2013–2016) of the Instituto de Salud Carlos III, by Fondos FEDER, by Fondos Regionales Gobierno del Principado de Asturias (Grupin 14/020), by Foundation of the University of Oviedo (FUO), and funds of University of Oviedo with “Programa de Apoyo y Promoción de la Investigación 2017,” by grant SeveroOcha 2013–2017 of the “Programa Estatal de Promoción del Talento y su Empleabilidad en I + D + I, Subprograma Estatal de Formación” and by Foundation “Nutrición y Crecimiento.”

Compliance with ethical standards

Written inform consent from the participants and approval of the hospital’s ethical committee were obtained.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.


Poster presentation in the 51st Annual Scientific Meeting of the European Society for Paediatric Nephrology (ESPN), on October 2018 in Belek, Antalya, Turkey.


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Copyright information

© IPNA 2019

Authors and Affiliations

  • Olaya Hernández-Frías
    • 1
  • Helena Gil-Peña
    • 2
  • José M. Pérez-Roldán
    • 2
  • Susana González-Sanchez
    • 2
  • Gema Ariceta
    • 3
  • Sara Chocrón
    • 3
  • Reyner Loza
    • 4
  • Francisco de la Cerda Ojeda
    • 5
  • Leire Madariaga
    • 6
  • Inés Vergara
    • 7
  • Marta Fernández-Fernández
    • 8
  • Susana Ferrando-Monleón
    • 9
  • Montserrat Antón-Gamero
    • 10
  • Ángeles Fernández-Maseda
    • 11
  • M. Isabel Luis-Yanes
    • 12
  • Fernando Santos
    • 1
    • 2
    • 13
    Email author return OK on get
  1. 1.University of OviedoOviedoSpain
  2. 2.Hospital Universitario Central de AsturiasOviedoSpain
  3. 3.Hospital Vall d’HebronBarcelonaSpain
  4. 4.Hospital Cayetano HerediaLimaPeru
  5. 5.Hospital Virgen del RocíoSevillaSpain
  6. 6.Hospital de CrucesVizcayaSpain
  7. 7.Complexo Hospitalario Universitario A CoruñaA CoruñaSpain
  8. 8.Complejo Asistencial Universitario de LeónLeónSpain
  9. 9.Hospital de la RiberaValenciaSpain
  10. 10.Hospital Universitario Reina SofíaMadridSpain
  11. 11.Hospital Virgen de la SaludToledoSpain
  12. 12.Hospital Universitario Nuestra Señora de CandelariaSanta Cruz de TenerifeSpain
  13. 13.Nefrología PediátricaHospital Universitario Central de AsturiasOviedoSpain

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