X-linked Hypophosphatemia and FGF21 (XLH 21)

X-linked Hypophosphatemia and Carbohydrate and Lipid Metabolism: a Role for FGF21?

Fibroblast Growth Factor 23 and Fibroblast Growth Factor 21 are two endocrine Fibroblast Growth Factors, requiring Klotho as a co-factor to promote their systemic actions. Fibroblast Growth Factor 21 is involved in the regulation of glucid and lipid metabolism. Fibroblast Growth Factor 21 Knock Out mice display obesity and hyperglycemia.

In investigators experience, patients with X-linked hypophosphatemia often present with early-onset over-weight that could be partly explained by decreased physical activity because of bone pains and deformations after puberty; however, patients usually display progressive over-weight earlier in life, when there is no limitation of physical activity yet.

To the knowledge of investigators the association between Fibroblast Growth Factor 23, Fibroblast Growth Factor 21 and Klotho in patients with X-linked hypophosphatemia has never been evaluated. Thus, the main objective of this study is to evaluate the glucid and lipid metabolism in patients with X-linked hypophosphatemia, the main working hypothesis being that the genetic deregulation in the Fibroblast Growth Factor 23 axis in patients with X-linked hypophosphatemia induces modifications of Klotho levels (namely decreased levels) that in turn will deregulate the Fibroblast Growth Factor 21 axis (resistance to Fibroblast Growth Factor 21 because of decreased Klotho levels).

Study Overview

• Status: Completed
• Conditions: X-linked Hypophosphatemia
• Intervention / Treatment: Other: Descriptive study

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Centre de Référence des Maladies Rénales Rares - Centre de Référence des Maladies Rares du Calcium et du Phosphate - Service de Néphrologie, Rhumatologie et Dermatologie Pédiatriques - Hôpital Femme Mère Enfant
  • Paris, France, 94270
    • Centre de Référence des Maladies Rares du Calcium et du Phosphore, Service d'Endocrinologie Pédiatrique - Hôpital du Kremlin Bicêtre
  • Toulouse, France, 31059
    • Endocrinologie, Maladies Osseuses, Gynécologie, Génétique, Hôpital des Enfants, CHU de Toulouse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 10 to 18 years followed in the different sites of the French Reference Center for Rare Diseases of Calcium and Phosphate, and monitored for hypophosphatemic rickets; estimated number to be included, N=40

Description

Inclusion Criteria:

• Child with X-linked hypophosphatemia with PHEX gene mutation
• Child between 10 and 18 years old
• Child over 10 kg having a blood sample as part of the treatment (due to regulatory constraints for blood volume taken in 30-day period of 40 mL in children over 10 kg)
• Child and parent / holder of parental authority who has been informed of the study and does not object to participate.

Exclusion Criteria:

- Pregnancy in progress

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Circulating FGF21	Samples specific to the study will be collected during a sampling performed as part of the usual care and follow-up of the patient. An additional tube (5 ml maximum) will be collected, which will be sent to the Lyon Sud Hospital Center for analysis of circulating FGF21.	1 day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2019
• Primary Completion (Actual): February 27, 2020
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: July 12, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Musculoskeletal Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Phosphorus Metabolism Disorders; Rickets; Vitamin D Deficiency; Rickets, Hypophosphatemic; Hypophosphatemia, Familial; Familial Hypophosphatemic Rickets; Hypophosphatemia
• Other Study ID Numbers: 69HCL18_0349; 2018-A01304-51 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No