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

Persistent Hyperparathyroidism: A Reality Calling for Additional Evidence

Editoriale AJKD Vol XX | Iss XX | Month 2022 In this issue of AJKD, Wang et al1 report on the incidence, trends, and consequences of treatment of posttransplant hyperparathyroidism in a nationwide registry encompassing 30,127 Medicare-insured US patients who received a first kidney transplant. …In clinical practice, we want to identify patients with negative … Leggi tutto

2 – Nephrocalcinosis and urolithiasis in children Kidney International (2012) 82, 493–497; doi:10.1038/ki.2012.142

Correction to: Kidney International (2011) 80:1278–1291; doi:10.1038/ki.2011.336 In the above-cited article, Table 2 was published with incorrect alignment of age ranges and erroneous unit changes concerning the cystine and urate excretion levels. The urate gram units needed to be multiplied by 10. In Table 1, the diagnosis related to NPT2a mutations should read ‘Urolithiasis, osteoporosis, … Leggi tutto

Hyperparathyroidism complicating CYP 24A1 mutations

CYP24A1 gene mutations induce infantile hypercalcemia, with high 1,25(OH)2D contrasting with low PTH levels. The adult phenotype is not well known. Two unrelated adult patients were referred for nephrolithiasis, hypertension, hypercalcemia, hypercalciuria, normal 25-OHD levels, and inappropriate PTH levels (22 to 92 pg/mL; N: 15–68) suggesting primary hyperparathyroidism, leading to surgery. Hypercalciuria improved despite persistent … Leggi tutto

Therapy‑Resistant Hypercalcemia in a Patient with Inactivating CYP24A1 Mutation and Recurrent Nephrolithiasis: Beware of Concomitant Hyperparathyroidism

We describe a case harboring a homozygous CYP24A1 mutation with mild loss of function, frst presenting with recurrent nephrolithiasis from the age of 22 onward, initially associated with hypercalcemia and low PTH concentrations. Over the years, hyperparathyroidism developed, resulting in more severe hypercalcemia. Also, kidney function deteriorated, most probably as a consequence of biopsy-proven nephrocalcinosis. … 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