Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake

Dinour, Dganit; Davidovits, Miriam; Aviner, Shraga; Ganon, Liat; Michael, Leonid; Modan‐Moses, Dalit; Vered, Iris; Bibi, Haim; Frishberg, Yaacov; Holtzman, Eliezer J.

doi:10.1007/s00467-014-2889-1

Cited by 76 publications

(66 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recently, hereditary absence of Cyp24a1 has been shown to lead to maternal and fetal hypercalcemia (249,820), likely because reduced catabolism of calcitriol leads to relatively unopposed actions of the active hormone to stimulate intestinal calcium absorption and potentially induce osteoclast-mediated bone resorption.…”

Section: Yu Etmentioning

confidence: 99%

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Kovacs

2016

Physiological Reviews

359

524

View full text Add to dashboard Cite

During pregnancy and lactation, female physiology adapts to meet the added nutritional demands of fetuses and neonates. An average full-term fetus contains ϳ30 g calcium, 20 g phosphorus, and 0.8 g magnesium. About 80% of mineral is accreted during the third trimester; calcium transfers at 300-350 mg/day during the final 6 wk. The neonate requires 200 mg calcium daily from milk during the first 6 mo, and 120 mg calcium from milk during the second 6 mo (additional calcium comes from solid foods). Calcium transfers can be more than double and triple these values, respectively, in women who nurse twins and triplets. About 25% of dietary calcium is normally absorbed in healthy adults. Average maternal calcium intakes in American and Canadian women are insufficient to meet the fetal and neonatal calcium requirements if normal efficiency of intestinal calcium absorption is relied upon. However, several adaptations are invoked to meet the fetal and neonatal demands for mineral without requiring increased intakes by the mother. During pregnancy the efficiency of intestinal calcium absorption doubles, whereas during lactation the maternal skeleton is resorbed to provide calcium for milk. This review addresses our current knowledge regarding maternal adaptations in mineral and skeletal homeostasis that occur during pregnancy, lactation, and post-weaning recovery. Also considered are the impacts that these adaptations have on biochemical and hormonal parameters of mineral homeostasis, the consequences for long-term skeletal health, and the presentation and management of disorders of mineral and bone metabolism.

show abstract

Section: Yu Etmentioning

confidence: 99%

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Kovacs

2016

Physiological Reviews

359

524

View full text Add to dashboard Cite

show abstract

“…The coding sequence and splice-sites of CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3, and SLC34A1 were amplified by PCR using intronic primers. Primers for CYP24A1 were previously described [3].…”

Section: Candidate Gene Sequencingmentioning

confidence: 99%

“…More recently, loss-of-function mutations of the CYP24A1 gene, encoding for the Vitamin D-24-hydroxylase, were discovered to be a main cause of severe infantile hypercalcemia, hypercalciuria and nephrocalcinosis [2], [3].…”

Section: Introductionmentioning

confidence: 99%

Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency

et al. 2016

Self Cite

View full text Add to dashboard Cite

BACKGROUND Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency. METHODS Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly. Functional studies were performed in Xenopus laevis oocytes and in transfected opossum kidney (OK) cells. RE-SULTS Our patient was identified as having nephrocalcinosis in utero, and at the age of 16.5 years, he had kidney insufficiency but no bone disease. Genetic analysis revealed a novel homozygous missense mutation, Arg215Gln, in SLC34A1, which encodes the renal sodium phosphate cotransporter NaPiIIa. Functional studies of the Arg215Gln mutant revealed reduced transport activity in Xenopus laevis oocytes and increased intracellular cytoplasmic accumulation in OK cells. CONCLUSIONS Our findings show that dysfunction of the human NaPiIIa causes severe renal calcification that may eventually lead to reduced kidney function, rather than complications of phosphate loss.

show abstract

“…Patients with bi-allelic mutations in CYP24A1 gene present with hypercalcemia, suppressed PTH levels and nephrocalcinosis in infancy [7,8,9,10,11,12] or nephrolithiasis in adulthood [8,11,13,14,15,16,17,18,19]. In the first report, Schlingmann et al [7], describe 8 CYP24A1 mutations in a cohort of 10 children from 8 unrelated families.…”

Section: Introductionmentioning

confidence: 99%

Mutational Spectrum of <b><i>CYP24A1</i></b> Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia

Gigante

Santangelo

Diella

et al. 2016

Nephron

View full text Add to dashboard Cite

Background/Aims: Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH). Methods: We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software. Results:CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls. Conclusion: To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms that CYP24A1 plays a causal role in some but not all cases of IIH (64%); (2) expands the spectrum of known CYP24A1 pathogenic mutations; (3) describes 2 hotspots detected in 50% of all Italian cases; and (4) emphasizes the importance of recognition and genetic diagnosis of CYP24A1 defects in infantile as well as adult hypercalcemia.

show abstract

Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake

Cited by 76 publications

References 17 publications

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency

Mutational Spectrum of <b><i>CYP24A1</i></b> Gene in a Cohort of Italian Patients with Idiopathic Infantile Hypercalcemia

Contact Info

Product

Resources

About