Bone and Mineral Metabolism

MON-755 - Clinical and biochemical characteristics of individuals with inactivating mutations of CYP24A1: a study of 13 families

Monday, June 15, 2026

9:00 AM - 2:00 PM CT

Senior Author/Primary Investigator(s)

EK

Eva Kassi, MD, PhD (she/her/hers)

Professor
Laiko General Hospital, National and Kapodistrian University of Athens
Athens, Greece

Co-Author(s)

MY

Maria P. Yavropoulou, MD, PhD

Laiko General Hospital, National and Kapodistrian University of Athens
Athens, Attiki, Greece
MC

Maria-Eleni Chondrogianni, MD

Laiko General Hospital, National and Kapodistrian University of Athens
Athens, Attiki, Greece
AR

Afroditi Roumpou, MD

Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens
Athens, Greece
AD

Artemis Doulgeraki, MD, PhD, MRCPCH, FRCPCH

Consultant Paediatrician
Institute of Child Health
Athens, Attiki, Greece
FP

Fotini Petichaki, MD

Laiko General Hospital, National and Kapodistrian University of Athens
Athens, Greece
SP

Stavroula A. Paschou, MD, PhD

Alexandra Hospital, School of Medicine, National & Kapodistrian University of Athens
Athens, Greece
EK

Efthymia Karlafti, Md, PhD

Medical School, National & Kapodistrian University of Athens, KAT Hospital
Athens, Greece
IT

Ioulia Trifonidi, n/a

KAT General Hospital
Athens, Greece
KM

Konstantinos Makris, PhD

KAT General Hospital
Athens, Greece
PL

Pierre Lukas, n/a

University of Liege, CHU de Liege
Liege, Belgium
EC

Etienne Cavalier, MD, PhD

University of Liege, CHU de Liege
Liege, Belgium
AP

Anna Papadopoulou, PhD

First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, ‘Aghia Sophia’ Children’s Hospital,
Athens, Greece

Late-Breaking Poster Presenter(s)

ST

SYMEON TOURNIS, MD, PhD

National and Kapodistrian University of Athens, KAT Hospital
Athens, Greece

Senior Author/Primary Investigator(s)

ST

SYMEON TOURNIS, MD, PhD

National and Kapodistrian University of Athens, KAT Hospital
Athens, Greece

Introduction
The CYP24A1 gene encodes 24-hydroxylase, an enzyme responsible for the inactivation of 1,25(OH)₂D and 25(OH)D through 24-hydroxylation. Biallelic loss-of-function mutations in CYP24A1 lead to idiopathic infantile hypercalcemia type 1 (HCINF1), characterized by PTH-independent hypercalcemia due to impaired vitamin D catabolism. Clinical presentation varies widely, ranging from severe infantile disease with vomiting, dehydration, and marked hypercalcemia to milder adult-onset forms presenting with hypercalcemia, hypercalciuria, or nephrolithiasis. Notably, heterozygous carriers may also exhibit clinical manifestations.
Aim
To describe the clinical and biochemical phenotype of individuals from 13 families with 24-hydroxylase deficiency.
Methods
This retrospective cohort study included 34 individuals (17 men, 17 women) from 13 families: 10 homozygotes, 4 compound heterozygotes, and 20 heterozygotes for CYP24A1 mutations. 25(OH)D and 24,25(OH)₂D were assessed using LC-MS/MS, FGF-23 using ELISA, and serum PTH, calcium, albumin, phosphorus, creatinine, 24h urine calcium, 1,25(OH)2DAdditionally, 25(OH)D and 24,25(OH)₂D levels were measured in 101 healthy controls. Group comparisons were performed using the Mann–Whitney U test. Continuous variables are presented as median (IQR).
Results
The mean age of affected individuals was 45.71±16.51 years (range 14–80), while controls had a mean age of 49.09±13.34 years. The most common variant was c.428_430delAAG (p.Glu143del) (26/34), followed by c.1186C>T (p.Arg396Trp) (n=8) and c.469C>T (p.Arg157Trp) (n=2).
The 25(OH)D/24,25(OH)₂D ratio was significantly higher in homozygous/compound heterozygous individuals [145.82 (116.44-168.75)] compared to heterozygotes [17.74 (14.24-19.80)], p< 0.001, and also differed between heterozygotes and controls (p=0.007). ROC analysis identified an optimal cutoff of 60.17, with 100% sensitivity and 95% specificity for identifying homozygous or compound heterozygous patients.
Homozygous/compound heterozygous individuals had significantly lower PTH levels [12.6 pg/ml (7.25-21) vs 32.8 (26-45.2); p< 0.001], and higher FGF23 levels [163.85 pg/ml (107.38-256.45) vs 73.21 (58.11-80.27); p< 0.001] than heterozygotes. 24h UCa excretion was also higher [349mg/24h (326-381) vs. 163 (156-278); p=0.005], while serum calcium levels did not differ significantly.
Nephrolithiasis or nephrocalcinosis was the most common clinical manifestation, affecting 17 patients, including five heterozygotes. Recurrent urinary tract infections were reported in four patients. Management was primarily conservative, with hydrochlorothiazide, rifampicin, or fluconazole used in selected cases.
Conclusion
Homozygous and compound heterozygous carriers of CYP24A1 mutations exhibit a more severe biochemical and clinical phenotype compared to heterozygous carriers.

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