CYP24A1 and SLC34A1 genetic defects associated with idiopathic infantile hypercalcemia: from genotype to phenotype

Loss of function mutations in the CYP24A1 gene, involved in vitamin D catabolism and in calcium homeostasis, are known to be the genetic drivers of both idiopathic infantile hypercalcemia (IIH) and adult renal stone disease. Recently, also defects in the SLC34A1 gene, encoding for the renal sodium-phosphate transporter NaPi-IIa, were associated with the disease. IIH … Leggi tutto

Hypercalcemia in Pregnancy Due to CYP24A1 Mutations: Case Report and Review of the Literature

Pathogenic mutations of CYP24A1 lead to an impaired catabolism of vitamin D metabolites and should be considered in the differential diagnosis of hypercalcemia with low parathyroid hormone concentrations. Diagnosis is based on a reduced 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio and confirmed by genetic analyses. Pregnancy is associated with an upregulation of the active vitamin … Leggi tutto

La carbamazepina antagonizza la soppressione di vitamina D-mediata dell’iperparatiroidismo secondario: patogenesi e possibilità terapeutiche

Carbamazepin antagonizes the vitamin D-mediated suppression of secondary hyperparathyroidism: pathogenesis and therapeutical options Abstract. This commentary updates: 1) the patophisiology responsible for carbamazepine-induced resistance to paricalcitol suppression of PTH in CKD; 2) the contribution of vitamin D deficiency to the adverse effects of carbamazepine; 3) the benefits of cholecalciferol supplementation either alone or in combination … Leggi tutto

Chronic hypercalcaemia from inactivating mutations of vitamin D 24-hydroxylase (CYP24A1): implications for mineral metabolism changes in chronic renal failure

Loss-of-function mutations of vitamin D-24 hydroxylase have recently been recognized as a cause of hypercalcaemia and nephrocalcinosis/nephrolithiasis in infants and adults. True prevalence and natural history of this condition are still to be defined.  … Probands had recurrent nephrolithiasis, chronic hypercalcaemia with depressed parathyroid hormone (PTH) and increased 1,25(OH)2D levels; carriers had nephrolithiasis (two of … Leggi tutto

Genetics of kidney stone disease

Kidney stone disease (nephrolithiasis) is a common problem that can be associated with alterations in urinary solute composition including hypercalciuria. Studies suggest that the prevalence of monogenic kidney stone disorders, including renal tubular acidosis with deafness, Bartter syndrome, primary hyperoxaluria and cystinuria, in patients attending kidney stone clinics is ∼15%. However, for the majority of … Leggi tutto

Genetics of kidney stone disease—Polygenic meets monogenic

Kidney stone disease comprising nephrolithiasis and nephrocalcinosis is a clinical syndrome of increasing prevalence with remarkable heterogeneity. Stone composition, age of manifestation, rate of recurrence, and impairment of kidney function varies with underlying etiologies. While calcium-based kidney stones account for the vast majority their etiology is still poorly understood. Recent studies underline the notion that … Leggi tutto

Metabolic Evaluation and Recurrence Prevention for Urinary Stone Patients: EAU Guidelines

Context: An optimum metabolic evaluation strategy for urinary stone patients has not been clearly defined. Objective: To evaluate the optimum strategy for metabolic stone evaluation and management to prevent recurrent urinary stones. Evidence acquisition: Several databases were searched to identify studies on the metabolic evaluation and prevention of stone recurrence in urolithiasis patients. Special interest … Leggi tutto

CYP3A4 Induction by Rifampin: An Alternative Pathway for Vitamin D Inactivation in Patients With CYP24A1 Mutations

 The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25- dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary … Leggi tutto