Related Experiment Video
Updated: May 4, 2026
Estimation of Urinary Nanocrystals in Humans using Calcium Fluorophore Labeling and Nanoparticle Tracking Analysis
Published on: February 9, 2021
A lifetime of hypercalcemia and hypercalciuria, finally explained
Thomas P Jacobs1, Martin Kaufman, Glenville Jones
1Division 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.
Insights
Genetic mutations in CYP24A1 can cause hypercalcemia, hypercalciuria, and kidney stones by impairing vitamin D metabolism. This case highlights a patient diagnosed with these conditions due to a homozygous CYP24A1 mutation.
Area of Science:
- Nephrology
- Endocrinology
- Genetics
Background:
- Hypercalcemia, hypercalciuria, and recurrent nephrolithiasis are common clinical issues.
- A novel cause for these conditions is presented in this case report.
Observation:
- A patient with a 30-year history of hypercalcemia, hypercalciuria, and nephrolithiasis was studied.
- Diagnosis was confirmed using advanced biochemical and genetic analyses.
Findings:
- Elevated calcium absorption (37.4%) and very low 24,25-dihydroxyvitamin D levels were observed.
- Genetic analysis revealed a homozygous E143del mutation in CYP24A1.
- Ketoconazole treatment improved serum calcium and renal function, unlike prednisone.
Implications:
- Mutations in CYP24A1 can lead to chronic hypercalcemia, hypercalciuria, and nephrolithiasis.
- These mutations impair the metabolism of 1,25-dihydroxyvitamin D, causing these conditions.
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.
More Related Videos
07:13Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation
Published on: March 14, 2017
11:30A Semi-Automated and Reproducible Biological-Based Method to Quantify Calcium Deposition In Vitro
Published on: June 2, 2022
Related Concept Videos
01:26Urinary Tract Calculi II: Pathophysiology and Clinical Manifestations
01:28Urinary Tract Calculi I: Introduction
01:21Skeleton and Calcium Homeostasis
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:27Urinary Tract Calculi IV: Nutrition Therapy and Prevention
01:30Urinary Tract Calculi III: Medical Management