Abstract
Mutations of the CYP24A1 gene, encoding for the enzyme 25(OH)D-24-hydroxylase, can cause hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis. We report the case of a 22-year-old male patient with recurrent nephrolithiasis, nephrocalcinosis, hypercalcemia with low parathyroid hormone levels, hypercalciuria and low bone mass. Gene sequencing showed that the patient had compound heterozygous mutations including a novel genotype of the CYP24A1 gene. Genetic CYP24A1 testing and biochemical analyses were offered to other family members; the father was heterozygous for the same novel genotype and was also affected with recurrent nephrolithiasis.
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References
Tebben PJ, Milliner DS, Horst RL et al (2012) Hypercalcemia, hypercalciuria, and elevated calcitriol concentrations with autosomal dominant transmission due to CYP24A1 mutations: effects of ketoconazole therapy. J Clin Endocrinol Metab 97(3):E423–E427
Schlingmann KP, Kaufmann M, Weber S et al (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365(5):410–421
Streeten EA, Zarbalian K, Damcott CM (2011) CYP24A1 mutations in idiopathic infantile hypercalcemia. N Engl J Med 365(18):1741–1743
Dauber A, Nguyen TT, Sochett E et al (2012) Genetic defect in CYP24A1, the vitamin D 24-hydroxylase gene, in a patient with severe infantile hypercalcemia. J Clin Endocrinol Metab 97(2):E268–E274
Castanet M, Mallet E, Kottler M-L (2013) Lightwood syndrome revisited with a novel mutation in CYP24 and vitamin D supplement recommendations. J Pediatr 163(4):1208–1210
Meusburger E, Mündlein A, Zitt E, Obermayer-Pietsch B, Kotzot D, Lhotta K (2013) Medullary nephrocalcinosis in an adult patient with idiopathic infantile hypercalcaemia and a novel CYP24A1 mutation. Clin Kidney J 6(2):211–215
Fencl F, Bláhová K, Schlingmann KP, Konrad M, Seeman T (2013) Severe hypercalcemic crisis in an infant with idiopathic infantile hypercalcemia caused by mutation in CYP24A1 gene. Eur J Pediatr 172(1):45–49
Dinour D, Beckerman P, Ganon L, Tordjman K, Eisenstein Z, Holtzman EJ (2013) Loss-of-function mutations of CYP24A1, the vitamin D 24-hydroxylase gene, cause long-standing hypercalciuric nephrolithiasis and nephrocalcinosis. J Urol 190(2):552–557
Nesterova G, Malicdan MC, Yasuda K et al (2013) 1,25-(OH)2D-24 hydroxylase (CYP24A1) deficiency as a cause of nephrolithiasis. Clin J Am Soc Nephrol CJASN 8(4):649–657
Colussi G, Ganon L, Penco S et al (2014) Chronic hypercalcaemia from inactivating mutations of vitamin D 24-hydroxylase (CYP24A1): implications for mineral metabolism changes in chronic renal failure. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc 29(3):636–643
Jacobs TP, Kaufman M, Jones G et al (2014) A lifetime of hypercalcemia and hypercalciuria, finally explained. J Clin Endocrinol Metab 99(3):708–712
Wolf P, Müller-Sacherer T, Baumgartner-Parzer S et al (2014) A case of “late-onset” idiopathic infantile hypercalcemia secondary to mutations in the CYP24A1 gene. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol 20(5):e91–e95
Dowen FE, Sayers JA, Hynes AM, Sayer JA (2014) CYP24A1 mutation leading to nephrocalcinosis. Kidney Int 85(6):1475
Figueres M-L, Linglart A, Bienaime F et al (2015) Kidney function and influence of sunlight exposure in patients with impaired 24-hydroxylation of vitamin D due to CYP24A1 mutations. Am J Kidney Dis Off J Natl Kidney Found 65(1):122–126
Molin A, Baudoin R, Kaufmann M et al (2015) CYP24A1 mutations in a cohort of hypercalcemic patients: evidence for a recessive trait. J Clin Endocrinol Metab 100(10):E1343–E1352
Cools M, Goemaere S, Baetens D et al (2015) Calcium and bone homeostasis in heterozygous carriers of CYP24A1 mutations: a cross-sectional study. Bone 81:89–96
Ketha H, Kumar R, Singh RJ (2016) LC-MS/MS for identifying patients with CYP24A1 mutations. Clin Chem 62(1):236–242
O’Keeffe DT, Tebben PJ, Kumar R, Singh RJ, Wu Y, Wermers RA (2016) Clinical and biochemical phenotypes of adults with monoallelic and biallelic CYP24A1 mutations: evidence of gene dose effect. Osteoporos Int 1–15. doi:10.1007/s00198-016-3615-6
Gigante M, Santangelo L, Diella S et al (2016) Mutational spectrum of CYP24A1 gene in a cohort of Italian patients with idiopathic infantile hypercalcemia. Nephron 133(3):193–204
Halbritter J, Baum M, Hynes AM et al (2015) Fourteen monogenic genes account for 15 % of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol 26(3):543–551
St-Arnaud R, Arabian A, Travers R et al (2000) Deficient mineralization of intramembranous bone in vitamin D-24-hydroxylase-ablated mice is due to elevated 1,25-dihydroxyvitamin D and not to the absence of 24,25-dihydroxyvitamin D. Endocrinology 141(7):2658–2666
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An erratum to this article is available at http://dx.doi.org/10.1007/s00240-016-0940-3.
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Ferraro, P.M., Minucci, A., Primiano, A. et al. A novel CYP24A1 genotype associated to a clinical picture of hypercalcemia, nephrolithiasis and low bone mass. Urolithiasis 45, 291–294 (2017). https://doi.org/10.1007/s00240-016-0923-4
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DOI: https://doi.org/10.1007/s00240-016-0923-4