TY - JOUR
T1 - 1,25-(OH)2D-24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis
AU - Nesterova, Galina
AU - Malicdan, May Christine
AU - Yasuda, Kaori
AU - Sakaki, Toshiyuki
AU - Vilboux, Thierry
AU - Ciccone, Carla
AU - Horst, Ronald
AU - Huang, Yan
AU - Golas, Gretchen
AU - Introne, Wendy
AU - Huizing, Marjan
AU - Adams, David
AU - Boerkoel, Cornelius F.
AU - Collins, Michael T.
AU - Gahl, William A.
PY - 2013/4/5
Y1 - 2013/4/5
N2 - Background and objectives 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. Design, setting, participants, & measurements 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. Results 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%. Conclusions The results of this study showthat 1,25(OH)2D-24-hydroxylase deficiency due to bi-allelicmutations in CYP24A1 causes elevated serum vitamin D, hypercalciuria, nephrocalcinosis, and renal stones.
AB - Background and objectives 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. Design, setting, participants, & measurements 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. Results 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%. Conclusions The results of this study showthat 1,25(OH)2D-24-hydroxylase deficiency due to bi-allelicmutations in CYP24A1 causes elevated serum vitamin D, hypercalciuria, nephrocalcinosis, and renal stones.
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U2 - 10.2215/CJN.05360512
DO - 10.2215/CJN.05360512
M3 - Article
C2 - 23293122
AN - SCOPUS:84876052295
SN - 1555-9041
VL - 8
SP - 649
EP - 657
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 4
ER -