Thomas P Jacobs1, Martin Kaufman, Glenville Jones, Rajiv Kumar, Karl-Peter Schlingmann, Sue Shapses, John P Bilezikian. 1. 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.
Abstract
CONTEXT: 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. DESIGN AND SETTING: This study consists of a case report and review of literature conducted in a University Referral Center. PATIENT AND INTERVENTION: A single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis was treated with low-calcium diet, low vitamin D intake, prednisone, and ketoconazole. MAIN OUTCOME MEASURE: 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.
CONTEXT: 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. DESIGN AND SETTING: This study consists of a case report and review of literature conducted in a University Referral Center. PATIENT AND INTERVENTION: A single patient with hypercalcemia, hypercalciuria, and recurrent nephrolithiasis was treated with low-calcium diet, low vitamin D intake, prednisone, and ketoconazole. MAIN OUTCOME MEASURE: 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.
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