Hypercalcemia due to CYP24A1 mutations: a systematic descriptive review

in European Journal of Endocrinology
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  • 1 Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
  • | 2 Statistic Analysis Unit, Department of Medicine and Oncology
  • | 3 Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy
  • | 4 Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

Correspondence should be addressed to F Cetani Email cetani@endoc.med.unipi.it
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Background and objectives

CYP24A1 encodes a 24-hydroxylase involved in vitamin D catabolism, whose loss-of-function results in vitamin D-dependent hypercalcemia. Since the identification of CYP24A1 variants as a cause of idiopathic infantile hypercalcemia, a large body of literature has emerged indicating heterogeneity in penetrance, symptoms, biochemistry, and treatments. The objectives of the present research work were to investigate the clinical heterogeneity of the disease, the possibility of a relevant phenotype for monoallelic carriers, and to compare the hypocalcemic effect of the available therapies.

Methods

Two reviewers searched different databases for studies published between the identification of CYP24A1 variants and December 31, 2020. Eligible studies included clinical trials and reports describing carriers of CYP24A1 variants.

Results

Fifty eligible studies were identified, accounting for 221 patients. Genetic data were retrieved and allele frequencies were calculated. Acute hypercalcemia was the typical presentation during the first year of life (76%, P = 0.0005), and nephrocalcinosis was more frequent in infancy (P < 0.0001). Pregnancy was associated with symptomatic hypercalcemia in 81.8% and high rates of obstetric complications. Monoallelic carriers displayed significant rates of nephrolithiasis (19.4%), nephrocalcinosis (4.9%), and symptomatic hypercalcemia (5.6%).

Conclusions

CYP24A1 loss-of-function results in an age-dependent phenotype, which can be exacerbated by triggering factors, such as pregnancy. Although biallelic carriers present more significant clinical and biochemical features, monoallelic carriers have an increased risk of calcium-related conditions. The highly variable tested therapeutic approaches did not allow to draw conclusions on preferable therapeutic regime.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
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