Abstract | BACKGROUND: METHODS: The genetic basis of a syndrome in a 44-yr-old Caucasian male characterized by intermittent hypercalcemia, hypercalciuria, elevated serum 1,25-dihydroxyvitamin D, undetectable serum 24,25-dihydroxyvitamin D, metabolically active nephrolithiasis, and reduced bone mineral density of the lumbar spine was examined. Sequencing of the CYP24A1 gene and biochemical and genetic analysis of seven family members in three generations was carried out. Because of hypercalcemia, hypercalciuria, and metabolically active nephrolithiasis, the patient was treated with a cytochrome 3A inhibitor, ketoconazole, 200 mg orally every 8 h, for 2 months. RESULTS: The sequence of the CYP24A1 gene showed two canonical splice junction mutations in the proband. Analysis of family members showed a phenotype associated one or both mutations, suggesting autosomal dominant transmission with partial penetrance of the trait. After therapy with ketoconazole, statistically significant reductions in previously elevated urinary calcium into the normal range were noted. Previously elevated serum 1,25-dihydroxyvitamin D and calcium concentrations decreased, and previously decreased PTH concentrations increased into the normal range, but the differences were not statistically significant. CONCLUSIONS:
|
Authors | Peter J Tebben, Dawn S Milliner, Ronald L Horst, Peter C Harris, Ravinder J Singh, Yanhong Wu, John W Foreman, Paul R Chelminski, Rajiv Kumar |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 97
Issue 3
Pg. E423-7
(Mar 2012)
ISSN: 1945-7197 [Electronic] United States |
PMID | 22337913
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 14-alpha Demethylase Inhibitors
- Steroid Hydroxylases
- CYP24A1 protein, human
- Vitamin D3 24-Hydroxylase
- Calcitriol
- Ketoconazole
|
Topics |
- 14-alpha Demethylase Inhibitors
(therapeutic use)
- Adult
- Calcitriol
(blood)
- Genotype
- Humans
- Hypercalcemia
(blood, drug therapy, genetics)
- Hypercalciuria
(blood, drug therapy, genetics)
- Ketoconazole
(therapeutic use)
- Male
- Mutation
- Steroid Hydroxylases
(genetics)
- Syndrome
- Treatment Outcome
- Vitamin D3 24-Hydroxylase
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|