Is CYP24A1 Heterozygosity a Risk Factor for Nephrolithiasis?
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Supplementary blood samples for PBMC analysis at V2.
- Who it may be relevant to
- Registry conditions: Nephrolithiasis. Basic parameters: 2 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Overview
Biallelic loss-of-function variants in CYP24A1 have been identified as a common genetic cause of autosomal recessive hypercalcemia (ARH, ORPHA 300547, 1 in 80,000 live births), characterized by low PTH (parathyroid hormone) levels, a high 25-OH D/24,25-(OH)₂D ratio, and susceptibility to vitamin D intoxication. In humans, heterozygous pathogenic variants in CYP24A1 have been proposed both as responsible for an autosomal dominant disorder and as a risk factor for nephrolithiasis, but the rarity and heterogeneity of human data prevent a definitive answer to this crucial question. Nephrolithiasis is a complex disease in which nutritional factors - particularly sodium and protein intake (leading to hypercalciuria) - play a key role. It also has a heritability of 50%, suggesting the involvement of many genetic susceptibility factors, as well as monogenic forms (mainly autosomal recessive, but also dominant or X-linked), which have been identified in 10-20% of patients. The increasing prevalence of nephrolithiasis, affecting approximately 10% of the general population over a lifetime, has a significant financial impact on healthcare systems and imposes a major burden of morbidity, justifying further investigation into the genetic underpinnings of nephrolithiasis. The goal of the HeteroCYP project is to improve understanding of the phenotypes associated with heterozygous, compound heterozygous, and homozygous variants of CYP24A1 by comparing clinical and biological outcomes in patients according to their mutation type
Interventions
- Biological Supplementary blood samples for PBMC analysis at V2
Supplementary blood (serum and plasma) and urines samples for bio collection at V3
Primary outcome measures
- Prevalence of nephrolithiasis in patients who are CYP24A1 heterozygous and homozygous (or compound heterozygous) [Time frame: Visit 2 (at least 24 hours after baseline)]
Eligibility criteria
Inclusion criteria
Group 1: Heterozygous Patients
- Aged between 2 and 90 years
- Weight > 12 kg
- Carriers of a heterozygous CYP24A1 mutation
- With or without symptoms: history of nephrocalcinosis or kidney stones
Group 2: Homozygous / Compound Heterozygous Patients
- Aged between 2 and 90 years
- Weight > 12 kg
- Carriers of a homozygous or compound heterozygous CYP24A1 mutation
- With or without symptoms: history of nephrocalcinosis or kidney stones
Exclusion criteria
- Individuals unable to collect 24-hour urine
- Individuals unable to be available for a full day in a day hospital (HDJ)
- Pregnant, postpartum, or breastfeeding women
- Individuals deprived of liberty by judicial or administrative decision
- Individuals receiving psychiatric care
- Individuals admitted to a healthcare or social institution for reasons other than participation in research
- Adults under legal protection (guardianship or trusteeship)
- Individuals not affiliated with a social security system or not benefiting from an equivalent scheme
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
France · 2 centers
- Hôpital Femme Mère Enfant — Bron
- Hôpital Edouard Herriot — Lyon
Identifiers
NCT: NCT07201701 · 69HCL25_0507 · 2025-A01749-40