title: Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake.
abstract: BACKGROUND
  Hypercalcemia is caused by many different conditions and may lead to severe complications. Loss-of-function mutations of CYP24A1, encoding vitamin D-24-hydroxylase, have recently been identified in idiopathic infantile hypercalcemia and in adult kidney stone disease. The aim of this study was to investigate the genetics and clinical features of both infantile and maternal hypercalcemia.
  
  
  METHODS
  We studied members of four unrelated Israeli families with hypercalcemia, namely, one woman during pregnancy and after delivery and three infants. Clinical and biochemical data were obtained from probands' medical charts. Genomic DNA was isolated from peripheral blood and CYP24A1 was sequenced.
  
  
  RESULTS
  Typical symptoms of hypercalcemia associated with the intake of recommended doses of vitamin D developed in the infants and pregnant woman. Four different loss-of-function CYP24A1 mutations were identified, two of which are reported here for the first time (p.Trp134Gly and p.Glu315*). The infants from families 1 and 2, respectively, were found to be compound heterozygotes, and the infant from family 3 and the pregnant woman were found to be homozygous.
  
  
  CONCLUSIONS
  This is the first report of maternal hypercalcemia caused by a CYP24A1 mutation, showing that not only infants are at risk for this complication. Our findings emphasize the importance of recognition, genetic diagnosis and proper treatment of this recently identified hypercalcemic disorder in this era of widespread vitamin D supplements.
authors.affiliation: Department of Nephrology and Hypertension, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 52621, Israel, Dganit.Dinour@sheba.health.gov.il.
authors.forename: Dganit
authors.initials: D
authors.lastname: Dinour
authors.forename: Miriam
authors.initials: M
authors.lastname: Davidovits
authors.forename: Shraga
authors.initials: S
authors.lastname: Aviner
authors.forename: Liat
authors.initials: L
authors.lastname: Ganon
authors.forename: Leonid
authors.initials: L
authors.lastname: Michael
authors.forename: Dalit
authors.initials: D
authors.lastname: Modan-Moses
authors.forename: Iris
authors.initials: I
authors.lastname: Vered
authors.forename: Haim
authors.initials: H
authors.lastname: Bibi
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Frishberg
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Holtzman
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D014807:Vitamin D / Q000008:administration & dosage; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D014815:Vitamins; D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase