Long-term Follow Op of Patients with Hypercalcemia\hypercalciuria due to CYP24A1 or SLC34A Mutations or Having Similar Biochemical Profile without Identified Mutation

Introduction: Infantile hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis are caused by dysregulation of calcium or phosphate homeostasis. Mutations in CYP24A1 and SLC34A genes encoding for vitamin D-24-hydroxylase and renal phosphate transporters NaPiIIa and NaPiIIc respectively lead to 1,25-vitamin-D elevation, absorptive hypercalcemia, PTH suppression, hypercalciuria and nephrocalcinosis.

The natural history of these conditions is still to be defined.

Goal and methods: Clinical and laboratory data and results of genetic evaluation were retrospectively retrieved from medical charts of 10 patients with above mentioned findings presented to Schneider’s pediatric nephrology institute between years 1998-2019 in order to describe the natural illness history.

Results: Median age at presentation was 6 (range 0-264) months, 6 patients were males, median follow up time was 4 (range 2.5-4) years. Mutations in CYP24A1, NaPiIIa and NaPiIIc were identified in 5, 1 and 1 patients respectively. Five patients presented with nephrocalcinosis, 3 with nephrolithiasis and 2 had normal renal US. High blood calcium and 1,25-D levels at presentation decreased during follow up (11,05±1 vs 9,9±0,5 mg\dl (p=0,012), 267,5±154 vs144±25 pmol\l (p=0.17), respectively), in parallel to increase in suppressed PTH levels (5,8±0,9 vs 11,8±7,3 pg\ml, p=0.2), 25-D levels were normal during follow up (71,89±18,7 nmol\l). Hypercalciuria at presentation was diagnosed in all patients except one who developed hypercalciuria after 2 years, in one hypercalciuria resolved after 4 years. All patients had normal GFR at presentation and at last follow up. Intervention included proper diet, citrate supplementation and thiazides.

Conclusion: Improvement of biochemical phenotype was shown in this cohort in long term follow up.