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

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

The study focuses on patients who are CYP24A1 heterozygous, CYP24A1 homozygous, or compound heterozygous.