Dataset Information

Hereditary Hypercalcemia Caused by a Homozygous Pathogenic Variant in the CYP24A1 Gene: A Case Report and Review of the Literature.

ABSTRACT:

Introduction

Loss of function mutations of CYP24A1 gene, which is involved in vitamin D catabolism, cause vitamin D-mediated PTH-independent hypercalcemia. The phenotype varies from life-threatening forms in the infancy to milder forms in the adulthood.

Case presentation

We report a case of a 17-year-old woman with a history of nephrolithiasis, mild PTH-independent hypercalcemia (10,5mg/dL), and high serum 1,25(OH)₂D concentrations (107pg/mL). Other causes of hypercalcemia associated with the above biochemical signature were excluded. Family history revealed nephrolithiasis in the sister. Blood testing in first-degree relatives showed serum PTH in the low-normal range and 1,25(OH)₂D at the upper normal limit or slightly elevated. The CYP24A1 gene analysis revealed a known homozygous loss-of-function pathogenic variant (c.428_430delAAG, rs777676129, p.Glu143del). The panel of vitamin D metabolites evaluated by liquid chromatography showed the typical profile of CYP24A1 mutations, namely, low 24,25(OH)₂D₃, elevated 25(OH)D₃:24,25(OH)₂D₃ ratio, and undetectable 1,24,25(OH)₃D₃. The parents and both the siblings harbored the same variant in heterozygosis. We decided for a watchful waiting approach and the patient remained clinically and biochemically stable over a 24-month followup.

Conclusion

CYP24A1 gene mutations should be considered in cases of PTH-independent hypercalcemia, once that more common causes (hypercalcemia of malignancy, granulomatous diseases, and vitamin D intoxication) have been ruled out.

SUBMITTER: Cappellani D

PROVIDER: S-EPMC6476011 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hereditary Hypercalcemia Caused by a Homozygous Pathogenic Variant in the <i>CYP24A1</i> Gene: A Case Report and Review of the Literature.

Cappellani Daniele D Brancatella Alessandro A Kaufmann Martin M Minucci Angelo A Vignali Edda E Canale Domenico D De Paolis Elisa E Capoluongo Ettore E Cetani Filomena F Jones Glenville G Marcocci Claudio C

Case reports in endocrinology 20190408

<h4>Introduction</h4>Loss of function mutations of CYP24A1 gene, which is involved in vitamin D catabolism, cause vitamin D-mediated PTH-independent hypercalcemia. The phenotype varies from life-threatening forms in the infancy to milder forms in the adulthood.<h4>Case presentation</h4>We report a case of a 17-year-old woman with a history of nephrolithiasis, mild PTH-independent hypercalcemia (10,5mg/dL), and high serum 1,25(OH)<sub>2</sub>D concentrations (107pg/mL). Other causes of hypercalce ...[more]

PMID: 31089432

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