Persistent Hypercalcemia Despite Parathyroidectomy for Primary Hyperparathyroidism in an Adult with Nephrocalcinosis and Nephrolithiasis Caused by a Novel Combination of Two Pathogenic CYP24A1 Mutations.

Hypercalcemia is a frequent electrolyte disorder with a wide range of possible causes. While primary hyperparathyroidism is one of the most frequent causes, loss-of-function mutations in the CYP24A1 gene, which encodes for the 24-hydroxylase enzyme responsible for the catabolism of 25(OH)D3 and 1,25(OH)2D3, have been described as a rare cause of hypercalcemia associated with nephrocalcinosis and nephrolithiasis due to the reduced degradation of vitamin D metabolites. We describe an interesting case of a 67-year-old woman who suffered from hypercalcemia with nephrocalcinosis and nephrolithiasis caused by the simultaneous presence of these two conditions. At the first presentation, primary hyperparathyroidism due to parathyroid adenoma was found to be causative, with partial parathyroidectomy leading to temporary normocalcemia. As hypercalcemia reappeared, an elevated 25(OH)D3/24,25(OH)2D3 ratio and consequently a novel combination of two pathogenic heterozygous missense mutations (c.1186C>T and c.628T>C) of the CYP24A1 gene were found. This case highlights the diagnostic complexity of persistent hypercalcemia and underscores the importance of also considering rare causes such as CYP24A1 mutations in the differential diagnosis after the exclusion of relevant frequent disease causes.