Hypercalciuria caused by CYP24A1 mutation: Fourteen years of the patient’s follow-up

Abstract

Introduction. Recently, inactivation mutations of CYP24A1, the gene encoding vitamin D 24-hydroxylase, were identified in hypercalciuric nephrolithiasis and nephrocalcinosis. Here, we describe ? long-term follow-up of a patient with hypercalciuric nephrolithiasis caused by CYP24A1 mutations. Case outline. A male Montenegro patient first presented with microhematuria at the age of five years. Hypercalciuria had been documented and for some time he had been treated by hydrochlorothiazide. After 12 years, the patient presented with macrohematuria and left-sided nephrolithiasis. He was found to have intermittent borderline hypercalcemia, suppressed parathyroid hormone, hypercalciuria, and increased plasma 25-hydroxy vitamin D [25(OH)D3]. The patient denied any vitamin D supplementation and all other causes of hypercalcemia were ruled out. Positive family history for nephrolithiasis (both parents and grandmother) and similar biochemical abnormalities detected in father and son pointed to an inherited disorder. A homozygous mutation in CYP24A1 (E143del) was found in the patient and his father, while mother is heterozygous. During the follow-up of two years, the patient underwent four extracorporeal shockwave lithotripsies, he was advised to increase water intake, and to avoid sunlight exposure. At the end of follow-up he was asymptomatic, and his renal ultrasound was normal, as well as his renal function, but hypercalciuria and low parathyroid hormone levels persisted. Conclusion. Hypervitaminosis D should be considered in children with idiopathic hypercalciuria, nephrolithiasis and nephrocalcinosis of unknown etiology. Recognition of CYP24A1 mutations in these patients may help to decrease the serious consequences by avoiding vitamin D supplements and excessive sun exposure.