Re: The diagnosis and management of hypercalcaemia
An important cause of hypercalcaemia that must not be forgotten (again).
As is pointed out by Minisola et al. (1) vitamin D preparations can cause toxicity leading to hypercalcaemia. A British outbreak of infantile idiopathic hypercalcaemia secondary to vitamin D supplementation of infant formula and fortified milk products occurred in the early 1950’s. This suggested that some individuals have an intrinsic hypersensitivity to vitamin D.
In a landmark paper Schlingmann et al (2) the molecular basis for idiopathic infantile hypercalcaemia was discovered to be secondary to mutations in CYP24A1. This enzyme normally inactivates 1,25-dihydroxyvitaminD3 and patients have a biochemical picture of hypercalcaemia, hypercalciuria and suppressed PTH. Recently mutations in CYP24A1 have been identified in adult patients with hypercalcaemia and suppressed PTH presenting with renal stones (3). These findings emphasise the importance of determining a history of vitamin D supplements / tanning bed use in patients who have hypercalcaemia (4), as such exposures may be sufficient to reveal an underlying molecular genetic defect in CYP24A1.
References
(1) Minisola S, Pepe J, Piemonte S, Cipriani C. The diagnosis and management of hypercalcaemia. BMJ 2015; 350:h2723
(2) Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365:410-21.
(3) Dinour D, Beckerman P, Ganon L, et al. Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis. J Urol. 2013;190:552-7
(4) Sayers J, Hynes AM, Srivastava S,Dowen F,Quinton R, Datta, HK, Sayer JA. Successful treatment of hypercalcaemia associated with a CYP24A1 mutation with fluconazole . Clinical Kidney Journal, 2015, 1-3.
Competing interests:
No competing interests
09 June 2015
John A. Sayer
Senior Clinical Lecturer in Nephrology
Newcastle Univeristy, UK
Institute of Genetic Medicine, Central Parkway, Newcastle NE13BZ, UK.
Rapid Response:
Re: The diagnosis and management of hypercalcaemia
An important cause of hypercalcaemia that must not be forgotten (again).
As is pointed out by Minisola et al. (1) vitamin D preparations can cause toxicity leading to hypercalcaemia. A British outbreak of infantile idiopathic hypercalcaemia secondary to vitamin D supplementation of infant formula and fortified milk products occurred in the early 1950’s. This suggested that some individuals have an intrinsic hypersensitivity to vitamin D.
In a landmark paper Schlingmann et al (2) the molecular basis for idiopathic infantile hypercalcaemia was discovered to be secondary to mutations in CYP24A1. This enzyme normally inactivates 1,25-dihydroxyvitaminD3 and patients have a biochemical picture of hypercalcaemia, hypercalciuria and suppressed PTH. Recently mutations in CYP24A1 have been identified in adult patients with hypercalcaemia and suppressed PTH presenting with renal stones (3). These findings emphasise the importance of determining a history of vitamin D supplements / tanning bed use in patients who have hypercalcaemia (4), as such exposures may be sufficient to reveal an underlying molecular genetic defect in CYP24A1.
References
(1) Minisola S, Pepe J, Piemonte S, Cipriani C. The diagnosis and management of hypercalcaemia. BMJ 2015; 350:h2723
(2) Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, et al. Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011;365:410-21.
(3) Dinour D, Beckerman P, Ganon L, et al. Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis. J Urol. 2013;190:552-7
(4) Sayers J, Hynes AM, Srivastava S,Dowen F,Quinton R, Datta, HK, Sayer JA. Successful treatment of hypercalcaemia associated with a CYP24A1 mutation with fluconazole . Clinical Kidney Journal, 2015, 1-3.
Competing interests: No competing interests