Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3159-e3166. doi: 10.1210/clinem/dgac315.
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.
We report clinical, biochemical, and imaging features of a 23-year-old man affected by HCINF1 with moderate hypercalcemia (12.9 mg/dL), symptomatic nephrolithiasis, nephrocalcinosis, and impaired kidney function [estimated glomerular filtration rate (eGFR) 60 mL/min/1.73 m2] treated with rifampin for an overall period of 24 months. Kidney, liver, and adrenal function were evaluated at every follow-up visit.
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 After 15 months, rifampin was temporally withdrawn because of asthenia, unrelated to impairment of adrenal function.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 a good safety profile.
由于 CYP24A1 基因的致病性变异，婴儿高钙血症 1 型（HCINF1）患者可能需要药物治疗来控制中重度高钙血症。利福平是一种抗结核药物，是细胞色素 P450 3 亚家族 A 成员 4（CYP3A4）的强力诱导剂，CYP3A4 参与维生素 D 的另一种代谢途径。先前有研究报道利福平改善高钙血症的疗效，但长期疗效和安全性仍存在许多问题。本研究旨在检验利福平治疗 HCINF1 患者的长期疗效和安全性。
我们报告了一位 23 岁男性患者的临床、生化和影像学特征。该患者患有 HCINF1，伴有中度高钙血症（12.9mg/dL）、症状性肾结石、肾钙质沉着症和肾功能受损（估算肾小球滤过率[eGFR]为 60mL/min/1.73m2），接受利福平治疗总时长为 24 个月。在每次随访时评估患者的肾脏、肝脏和肾上腺功能。
在 2 个月内，利福平使血清钙恢复正常（9.6mg/dL），同时肾功能改善（eGFR 为 92mL/min/1.73m2），治疗期间一直保持稳定。在 15 个月后，因乏力暂时停用利福平，乏力与肾上腺功能不全无关。3 个月后，将药物给药时间从早上改为晚上，乏力得到缓解。随访结束时，肾结石消失，肾钙质沉着症稳定。
利福平可能是一种有效的治疗选择，可稳定降低 HCINF1 患者的血钙水平，且安全性良好。
