Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene

Fencl, Filip; Bláhová, Květa; Schlingmann, Karl Peter; Konrad, Martin; Seeman, Tomáš

doi:10.1007/s00431-012-1818-1

Cited by 56 publications

(24 citation statements)

References 14 publications

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“…An additional report described two splice site mutations in another family [10]. Recently another child, which was homozygous for the R396W mutation already reported by Schlingmann et al , was described [11]. This patient suffered from severe hypercalcaemia at 4 months of age, which required haemofiltration to lower serum calcium.…”

Section: Discussionmentioning

confidence: 97%

Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation

Meusburger

Mündlein

Zitt

et al. 2013

Clinical Kidney Journal

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Idiopathic infantile hypercalcaemia (IIH) is an autosomal recessively inherited disease, presented in the first year of life with hypercalcaemia, precipitated by normal amounts of vitamin D supplementation. Recently loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-metabolizing enzyme 24-hydroxylase, have been found in these patients. We describe a young man homozygous for a novel missense mutation (c.628T>C) of the CYP24A1 gene. He had suffered from severe hypercalcaemia in early childhood. At age 29 he presented with medullary nephrocalcinosis, chronic kidney disease (CKD) stage 2, microalbuminuria, mild hypertension and nephrogenic diabetes insipidus. He had mild hypercalcaemia and moderate hypercalciuria. As a novel finding, fibroblast growth factor 23 (FGF23) was elevated.

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Section: Discussionmentioning

confidence: 97%

Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation

Meusburger

Mündlein

Zitt

et al. 2013

Clinical Kidney Journal

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“…Cependant, ceci reste à discuter puisque, si aucun des enfants supplémenté n'avait une concentration de vitamine D supérieure aux concentrations toxiques (250 nmol/L[25]), nous n'avons pas mesuré la calciurie. En effet, la supplémentation préventive collective pourrait induire chez des enfants hyper-sensibles à la vitamine D, notamment par mutation du gène de le 24-hydroxylase une hypercalcémie ou une hypercalciurie avec néphrocalci-nose malgré des concentrations plasmatiques en 25(OH)D normales[26][27][28]. Ceci pourrait être d'autant plus probléma-tique que l'incidence de cette hypersensibilité n'est pas connue et que les complications peuvent survenir avec des apports normaux de vitamine D et possiblement de façon prolongée[29].…”

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Prévalence du déficit en vitamine D chez les enfants âgés de 5 à 10ans en Bretagne Occidentale

Beuzit

L’hour

Roudaut

et al. 2015

Archives de Pédiatrie

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“…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%

“…In the first report, Schlingmann et al [7], describe 8 CYP24A1 mutations in a cohort of 10 children from 8 unrelated families. Additional case reports [8,9,10,11,12,13,14,15,16,17,18] from several European and American research groups describing at most 7 patients reported novel missense, nonsense, frameshift and splicing mutations [8,11,12,13,14,15,16,17,18] spread along the whole length of the gene. Recently, Molin et al [19] screened for CYP24A1 mutations one of the first large cohort of patients (n = 72) with hypercalcemia and low PTH levels, reporting bi-allelic variations in 20/72 patients (28%) and describing 15 new pathogenic mutations.…”

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

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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.

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Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene

Cited by 56 publications

References 14 publications

Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation

Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation

Prévalence du déficit en vitamine D chez les enfants âgés de 5 à 10ans en Bretagne Occidentale

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

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