Long-term Efficacy and Safety of Rifampin in the Treatment of a Patient Carrying a CYP24A1 Loss-of-Function Variant

Pharmacological therapy may be useful in the treatment of moderate to severe hypercalcemia in patients with infantile hypercalcemia-1 (HCINF1) due to pathogenic variants in the cytochrome P450 24 subfamily A member 1 (CYP24A1). Rifampin is an antituberculosis drug that is a potent inducer of cytochrome P450 3 subfamily A member 4, which is involved in an alternative catabolic pathway of vitamin D. The efficacy of rifampin in improving hypercalcemia was previously reported, but many questions remain on the long-term efficacy and safety. The aim of the study is to test the long-term efficacy and safety of rifampin in a patient with HCINF1. : In 2 months, rifampin induced a normalization of serum calcium (9.6 mg/dL) associated with an improvement of kidney function (eGFR 92 mL/min/1.73 m2 ) stable during the treatment. After 15 months, rifampin was temporally withdrawn because of asthenia, unrelated to impairment of adrenal function. After 3 months, the timing of drug administration was shifted from the morning to the evening, obtaining the remission of asthenia. At the end of follow-up, the nephrolithiasis disappeared and the nephrocalcinosis was stable. Rifampin could represent an effective choice to induce a stable reduction of calcium levels in patients with HCINF1, with….


AUTORE: Alessandro Brancatella, Daniele Cappellani, Martin Kaufmann, Antonella Semeraro, Simona Borsari, Chiara Sardella, Fulvia Baldinotti, Maria Adelaide Caligo, Glenville Jones, Claudio Marcocci, Filomena Cetani.