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-p...

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Bibliographic Details
Published in:	Clinical chemistry and laboratory medicine Vol. 57; no. 11; p. 1650
Main Authors:	De Paolis, Elisa, Scaglione, Giovanni Luca, De Bonis, Maria, Minucci, Angelo, Capoluongo, Ettore
Format:	Journal Article
Language:	English
Published:	Germany 25-10-2019
Subjects:	Genotype Humans Hypercalcemia - enzymology Hypercalcemia - genetics Mutation Phenotype Sodium-Phosphate Cotransporter Proteins, Type IIa - genetics Vitamin D3 24-Hydroxylase - genetics Vitamin D3 24-Hydroxylase - metabolism phosphate CYP24A1 calcium SLC34A1 vitamin D idiopathic infantile hypercalcemia
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Summary:	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 typically affects infants and pediatric patients with a syndrome characterized by severe hypercalcemia, hypercalciuria, suppressed parathyroid hormone level and nephrolithiasis. In SLC34A1 mutated carriers, hypophosphatemia is also a typical biochemical tract. IIH may also persist undiagnosed into adulthood, causing an increased risk of nephrocalcinosis and renal complication. To note, a clinical heterogeneity characterizes IIH manifestation, principally due to the controversial gene-dose effect and, to the strong influence of environmental factors. The present review is aimed to provide an overview of the current molecular findings on the IIH disorder, giving a comprehensive description of the association between genotype and biochemical and clinical phenotype of the affected patients. We also underline that patients may benefit from genetic testing into a targeted diagnostic and therapeutic workflow.
ISSN:	1437-4331
DOI:	10.1515/cclm-2018-1208