Details

Autor(en) / Beteiligte

• Nesterova, Galina
• Malicdan, May Christine
• Yasuda, Kaori
• Sakaki, Toshiyuki
• Vilboux, Thierry
• Ciccone, Carla
• Horst, Ronald
• Huang, Yan
• Golas, Gretchen
• Introne, Wendy
• Huizing, Marjan
• Adams, David
• Boerkoel, Cornelius F
• Collins, Michael T
• Gahl, William A

Titel

1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis

Ist Teil von

• Clinical journal of the American Society of Nephrology, 2013-04, Vol.8 (4), p.649-657

Ort / Verlag

United States: American Society of Nephrology

Erscheinungsjahr

2013

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Elevated serum vitamin D with hypercalciuria can result in nephrocalcinosis and nephrolithiasis. This study evaluated the cause of excess 1,25-dihydroxycholecalciferol (1α,25(OH)2D3) in the development of those disorders in two individuals. Two patients with elevated vitamin D levels and nephrocalcinosis or nephrolithiasis were investigated at the National Institutes of Health (NIH) Clinical Center and the NIH Undiagnosed Diseases Program, by measuring calcium, phosphate, and vitamin D metabolites, and by performing CYP24A1 mutation analysis. Both patients exhibited hypercalciuria, hypercalcemia, low parathyroid hormone, elevated vitamin D (1α,25(OH)2D3), normal 25-OHD3, decreased 24,25(OH)2D, and undetectable activity of 1,25(OH)2D-24-hydroxylase (CYP24A1), the enzyme that inactivates 1α,25(OH)2D3. Both patients had bi-allelic mutations in CYP24A1 leading to loss of function of this enzyme. On the basis of dbSNP data, the frequency of predicted deleterious bi-allelic CYP24A1 variants in the general population is estimated to be as high as 4%-20%. The results of this study show that 1,25(OH)2D-24-hydroxylase deficiency due to bi-allelic mutations in CYP24A1 causes elevated serum vitamin D, hypercalciuria, nephrocalcinosis, and renal stones.