title: A lifetime of hypercalcemia and hypercalciuria, finally explained.
abstract: BACKGROUND
  Hypercalcemia, hypercalciuria, and recurrent nephrolithiasis are all common clinical problems. This case report illustrates a newly described but possibly not uncommon cause of this presenting complex.
  
  
  OBJECTIVE
  We report on a patient studied for over 30 years, with the diagnosis finally made with modern biochemical and genetic tools.
  
  
  METHODS
  This study consists of a case report and review of literature conducted in a University Referral Center.
  
  
  METHODS
  A single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis was treated with low-calcium diet, low vitamin D intake, prednisone, and ketoconazole.
  
  
  METHODS
  We measured the patient's clinical and biochemical response to interventions above.
  
  
  RESULTS
  Calcium absorption measured by dual isotope absorptiometry was elevated at 37.4%. Serum levels of 24,25-dihydroxyvitamin D were very low, as measured in two laboratories (0.62 ng/mL [normal, 3.49 ± 1.57], and 0.18 mg/mL). Genetic analysis of CYP24A1 revealed homozygous mutation E143del previously described. The patient's serum calcium and renal function improved markedly on treatment with ketoconazole but not with prednisone.
  
  
  CONCLUSIONS
  Chronic hypercalcemia, hypercalciuria, and/or nephrolithiasis may be caused by mutations in CYP24A1 causing failure to metabolize 1,25-dihydroxyvitamin D.
authors.affiliation: Division of Endocrinology (T.P.J., J.P.B.), Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032; Department of Biomedical and Molecular Sciences (M.K., G.J.), Queen's University, Kingston, Ontario, Canada K7L 3N6; Nephology Research (R.K.), Departments of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55902; Department of General Pediatrics (K.-P.S.), University Children's Hospital, 48129 Munster, Germany; and School of Environmental and Biological Sciences (S.S.), Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Jacobs
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufman
authors.forename: Glenville
authors.initials: G
authors.lastname: Jones
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Karl-Peter
authors.initials: KP
authors.lastname: Schlingmann
authors.forename: Sue
authors.initials: S
authors.lastname: Shapses
authors.forename: John P
authors.initials: JP
authors.lastname: Bilezikian
mesh_terms: D000368:Aged; D003221:Confusion / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D057210:Delayed Diagnosis; D005221:Fatigue / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D053565:Hypercalciuria / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D006973:Hypertension / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D008297:Male; D053040:Nephrolithiasis / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D012008:Recurrence; D013250:Steroid Hydroxylases / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase