Biallelic CYP24A1 variants presenting during pregnancy: clinical and biochemical phenotypes.
CYP24A1 mutation
genetic mutation
hypercalcaemia
hypervitaminosis D
phenotype
vitamin D
Journal
Endocrine connections
ISSN: 2049-3614
Titre abrégé: Endocr Connect
Pays: England
ID NLM: 101598413
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
06
04
2020
accepted:
06
05
2020
pubmed:
7
5
2020
medline:
7
5
2020
entrez:
7
5
2020
Statut:
ppublish
Résumé
Inactivating mutations in CYP24A1, encoding vitamin D-24-hydroxylase, can lead to an accumulation of active vitamin D metabolites and consequent hypercalcaemia. Patient (infantile and adult) presentation is varied and includes mild-severe hypercalcaemia, hypercalciuria, nephrocalcinosis and nephrolithiasis. This study aimed to characterize the clinical and biochemical phenotypes of a family with two CYP24A1 missense variants. The proband and seven family members underwent detailed clinical and biochemical evaluation. Laboratory measurements included serum calcium, intact parathyroid hormone (iPTH), vitamin D metabolites and urine calcium and creatinine. The proband presented during the second trimester of a planned pregnancy with flu-like symptoms. Laboratory tests showed elevated adjusted calcium of 3.27 (upper reference limit (URL: 2.30) mmol/L), suppressed iPTH (<6 ng/L), elevated 25(OH)D (264 (URL: 55) nmol/L) and elevated 1,25(OH)D (293 (URL: <280) pmol/L). Ionized calcium was 1.55 (URL: 1.28) mmol/L. Sanger sequencing revealed two heterozygous missense variants in the CYP24A1: p.(Arg439Cys), R439C and p.(Trp275Arg), W275R. The proband's brother and sister had the same genotype. The brother had intermittent hypercalcaemia and hypervitaminosis D. Only the sister had a history of nephrolithiasis. The proband's daughter and two nephews were heterozygous for the R439C variant. The proband and her brother frequently had elevated 25(OH)D:24,25(OH)2D ratios (>50) during follow-up. W275R is a new pathogenic CYP24A1 mutation in compound heterozygotic form with R439C in this family.
Identifiants
pubmed: 32375123
doi: 10.1530/EC-20-0150
pii: EC-20-0150
pmc: PMC7354719
doi:
pii:
Types de publication
Journal Article
Langues
eng
Pagination
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