POS-443 AN UNUSUAL TREATMENT FOR 1,25 DIHYDROXY VITAMIN D3 - 24 HYDROXYLASE DEFICIENCY INDUCED HYPERCALCIURIA - CASE REPORT

Abstract

Vitamin D metabolism plays a crucial role in calcium homeostasis. Not only overproduction of 1,25(OH) Vitamin D3 can lead to hypercalcemia and hypercalciuria, but lack of degradation too. It is now well known that inactivating mutations in Vitamin D3 24 hydroxylase (CYP24A1) are associated with hypercalcemia, hypercalciuria and stone formation by reducing the degradation of 25(OH) and 1,25(HO) Vitamin D3. We here describe a patient in whom such mutations were associated with multiple calcium stones in the kidneys. A treatment with oral Hypericum perforatum (St-John’s Wort) to promote 1,25(OH) Vitamin D3 degradation through induction of CYP3A4 was proposed. This is the first case reporting the use of St-John’s Wort to treat hypercalciuria secondary to CYP24A1 deficiency. Descriptive report of the patient clinical characteristics and history will be provided. Laboratory results including calcium levels, vitamin D and its metabolites levels, 24-hour urine collection before and after St-John’s Wort supplementation will be described. A 35-year-old Caucasian male known for familial hypercalciuria was evaluated for a history of renal stone formation that had begun more than 10 years previously. Laboratory tests revealed mild hypercalcemia with hypercalciuria (9,1 mmol/day), normal serum levels of phosphorus, 25(OH) Vitamin D3 and 1,25(OH)2 Vitamin D3 and very low or undetectable serum levels of PTH, PTHrP and 24,25(OH)2 Vitamin D3 serum levels. Genetic testing also revealed a homozygous pathogenic mutation in CYP24A1 (NM_000782.4: c.400T>G; p.Trp134Gly) as the cause of hypercalciuria in this case. While the patient refused to be treated with ketoconazole, an 1-alpha hydroxylase inhibitor, he accepted to try the St-John’s Wort extracts (300 mg tid), a CYP3A4 inducer that is also involved in 25(OH) Vitamin D3 and 1,25(OH)2 vitamin D3 degradation (Fig. 1). To our surprise, this treatment led calciuria to decrease from 9,1 to 3,8 mmol/day after a few weeks. To our knowledge, this is the first report of the use of St-John’s Wort supplementation to reduce calciuria in a patient genetically inactivated for CYP24A1 This observation could pave the way towards the use of St-John’s Wort in the treatment of hypercalciuric renal stone disease of different causes in other patients. Moreover, this therapeutic option does not bear the serious adverse effects of other therapy, namely: androgen deficit induced by ketoconazole and positive calcium balance with thiazide diuretics.