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

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-y...

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Detalles Bibliográficos
Autores principales: Cappellani, Daniele, Brancatella, Alessandro, Kaufmann, Martin, Minucci, Angelo, Vignali, Edda, Canale, Domenico, De Paolis, Elisa, Capoluongo, Ettore, Cetani, Filomena, Jones, Glenville, Marcocci, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476011/
https://www.ncbi.nlm.nih.gov/pubmed/31089432
http://dx.doi.org/10.1155/2019/4982621
Descripción
Sumario: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)(2)D 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)(2)D 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)(2)D(3), elevated 25(OH)D(3):24,25(OH)(2)D(3) ratio, and undetectable 1,24,25(OH)(3)D(3). 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.