Dent’s disease is an X-linked renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis or nephrolithiasis. The disease is caused by mutations in a renal chloride channel gene, CLCN5. We report on three boys, of Indian origin, with Dent’s disease that presented at an early age (1–4 years), with polyuria, polydipsia, salt craving, recurrent vitamin A-responsive night blindness, hypophosphataemic rickets, hypercalciuria and low molecular weight proteinuria. All these patients were found to have novel mutations in the CLCN5 gene.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Pook MA, Wrong O, Wooding C, Norden AG, Feest TG, Thakker RV (1993) Dent’s disease, a renal Fanconi syndrome with nephrocalcinosis and kidney stones, is associated with a microdeletion involving DXS255 and maps to Xp11.22. Hum Mol Genet 2:2129–2134
Wrong OM, Norden AG, Feest TG (1994) Dent’s disease: a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive renal failure and a marked male predominance. QJM 87:473–493
Thakker RV (1998) The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis. Curr Opin Nephrol Hypertens 7:385–388
Frymoyer PA, Scheinman SJ, Dunham PB, Jones DB, Hueber P, Schroeder ET (1991) X-linked recessive nephrolithiasis with renal failure. N Engl J Med 325:681–686
Bolino A, Devoto M, Enia G, Zoccali C, Weissenbach J, Romeo G (1993) Genetic mapping in the Xp11.2 region of a new form of X-linked hypophosphatemic rickets. Eur J Hum Genet 1:269–279
Igarashi T, Gunther W, Sekine T, Inatomi J, Shiraga H, Takahashi S, Suzuki J, Tsuru N, Yanagihara T, Shimazu M, Jentsch TJ, Thakker RV (1998) Functional characterization of renal chloride channel, CLCN5, mutations associated with Dent’s Japan disease. Kidney Int 54:1850–1856
Morimoto T, Uchida S, Sakamoto H, Kondo Y, Hanamizu H, Fukui M, Tomino Y, Nagano N, Sasaki S, Marumo F (1998) Mutations in CLCN5 chloride channel in Japanese patients with low molecular weight proteinuria. J Am Soc Nephrol 9:811–818
Lloyd SE, Gunther W, Pearce SH, Thomson A, Bianchi ML, Bosio M, Craig IW, Fisher SE, Scheinman SJ, Wrong O, Jentsch TJ, Thakker RV (1997) Characterization of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders. Hum Mol Genet 6:1233–1239
Fisher SE, van Bakel I, Lloyd SE, Pearce SH, Thakker RV, Craig IW (1995) Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis). Genomics 29:598–606
Jentsch TJ, Friedrich T, Schriever A, Yamada H (1999) The CLC chloride channel family. Pflugers Arch 437:783–795
Woitas RP, Stoffel-Wagner B, Poege U, Schiedermaier P, Spengler U, Sauerbruch T (2001) Low-molecular weight proteins as markers for glomerular filtration rate. Clin Chem 47:2179–2180
Ludwig M, Doroszewicz J, Seyberth HW, Bökenkamp A, Balluch B, Nuutinen M, Utsch B, Waldegger S (2005) Functional evaluation of Dent’s disease-causing mutations: implications for ClC-5 channel trafficking and internalization. Hum Genet 117:228–237
Cheong HI, Lee JW, Zheng SH, Lee JH, Kang JH, Kang HG, Ha IS, Lee SJ, Choi Y (2005) Phenotype and genotype of Dent’s disease in three Korean boys. Pediatr Nephrol 20:455–459
Tosetto E, Ghiggeri GM, Emma F, Barbano G, Carrea A, Vezzoli G, Torregrossa R, Cara M, Ripanti G, Ammenti A, Peruzzi L, Murer L, Ratsch IM, Citron L, Gambaro G, D’angelo A, Anglani F (2006) Phenotypic and genetic heterogeneity in Dent’s disease—the results of an Italian collaborative study. Nephrol Dial Transplant 21:2452–2463
Hoopes RR Jr, Raja KM, Koich A, Hueber P, Reid R, Knohl SJ, Scheinman SJ (2004) Evidence for genetic heterogeneity in Dent’s disease. Kidney Int 65:1615–1620
WHO global database on vitamin A deficiency (2007) https://doi.org/who.int/vmnis/vitamina/data/database/countries/ind_vita.pdf (updated 6 December 2007; cited 10 February 2009)
Norden AG, Scheinman SJ, Deschodt-Lanckman MM, Lapsley M, Nortier JL, Thakker RV, Unwin RJ, Wrong O (2000) Tubular proteinuria defined by a study of Dent’s (CLCN5 mutation) and other tubular diseases. Kidney Int 57:240–249
Strom TM, Nyakatura G, Apfelstedt-Sylla E, Hellebrand H, Lorenz B, Weber BHF, Wutz K, Gutwillinger N, Ruether K, Drescher B, Sauer C, Zrenner E, Meitinger T, Rosenthal A, Meindl A (1998) An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. Nat Genet 19:260–263
Devuyst O, Christie PT, Courtoy PJ, Beauwens R, Thakker RV (1999) Intra-renal and subcellular distribution of the human chloride channel, CLC-5, reveals a pathophysiological basis for Dent’s disease. Hum Mol Genet 8:247–257
Ghoshal AK, Soldin SJ (2003) Evaluation of the Dade Behring Dimension RxL: integrated chemistry system—pediatric reference ranges. Clin Chim Acta 331:135–146
Pia Uerdingen is acknowledged for excellent technical assistance.
S.K. Sethi and M. Ludwig contributed equally to the manuscript.
About this article
Cite this article
Sethi, S.K., Ludwig, M., Kabra, M. et al. Vitamin A responsive night blindness in Dent’s disease. Pediatr Nephrol 24, 1765–1770 (2009). https://doi.org/10.1007/s00467-009-1198-6
- Hypophosphataemic rickets
- Night blindness
- Dent’s disease