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: