"Dent's disease" is often used to describe an entire group of familial disorders, including X-linked recessive nephrolithiasis with kidney failure, X-linked recessive hypophosphatemic rickets, and both Japanese and idiopathic low-molecular-weight proteinuria.[2] About 60% of patients have mutations in the CLCN5 gene (Dent 1), which encodes a kidney-specific chloride/proton antiporter, and 15% of patients have mutations in the OCRL1 gene (Dent 2).[3]
Hyperuricosuria (excessive amounts of uric acid in the urine)
Impaired urinary acidification
Rickets
In a study of 25 patients with Dent's disease,[5] 9 of 15 men, and one of 10 women had end-stage kidney disease by the age of 47.[6]
Geneticsedit
X-linked recessive inheritanceThree-dimensional homology model of human CLC-5 based on the structure of ClC-ec1 (7) showing the locations of each mutated residue
Dent disease 1edit
Dent's disease is a X-linked recessive disorder. The males are prone to manifesting symptoms in early adulthood with symptoms of calculi, rickets or even with kidney failure in more severe cases.[4]
In humans, gene CLCN5 is located on chromosome Xp11.22, and has a 2238-bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746-amino-acid protein.[7]CLCN5 belongs to the family of voltage-gated chloride channel genes (CLCN1-CLCN7, CLCKa and CLCKb) that have about 12 transmembrane domains. These chloride channels have an important role in the control of membrane excitability, transepithelial transport, and possibly cell volume.[8]
The mechanisms by which CLC-5 dysfunction results in hypercalciuria and the other features of Dent's disease remain to be elucidated. The identification of additional CLCN5 mutations may help in these studies.[9]
Dent disease 2edit
Dent disease 2 (nephrolithiasis type 2) is associated with the OCRL gene.[10][11] Both Lowe syndrome (oculocerebrorenal syndrome) and Dent disease can be caused by truncating or missense mutations in OCRL.
Diagnosisedit
Diagnosis is based on genetic study of CLCN5 gene.[citation needed]
Treatmentedit
As of today, no agreed-upon treatment of Dent's disease is known and no therapy has been formally accepted. Most treatment measures are supportive in nature:
In rats with diabetes insipidus, thiazide diuretics inhibit the NaCl cotransporter in the renal distal convoluted tubule, leading indirectly to less water and solutes being delivered to the distal tubule.[12] The impairment of Na transport in the distal convoluted tubule induces natriuresis and water loss, while increasing the reabsorption of calcium in this segment in a manner unrelated to sodium transport.
Amiloride also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria.
A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dent's patients, but urine pH was "significantly higher in patients with Dent's disease than in those with idiopathic hypercalciuria (P < 0.03), and supersaturation for uric acid was consequently lower (P < 0.03)."[13]
For patients with osteomalacia, vitamin D or derivatives have been employed, apparently with success.
Some lab tests on mice with CLC-5-related tubular damage showed a high-citrate diet preserved kidney function and delayed progress of kidney disease.[14]
Historyedit
Dent's disease was first described by Charles Enrique Dent and M. Friedman in 1964, when they reported two unrelated British boys with rickets associated with renal tubular damage characterized by hypercalciuria, hyperphosphaturia, proteinuria, and aminoaciduria.[15] This set of symptoms was not given a name until 30 years later, when the nephrologist Oliver Wrong more fully described the disease.[5] Wrong had studied with Dent and chose to name the disease after his mentor.[16] Dent's disease is a genetic disorder caused by mutations in the gene CLCN5, which encodes a kidney-specific voltage-gated chloride channel, a 746-amino-acid protein (CLC-5) with 12 to 13 transmembrane domains. It manifests itself through low-molecular-weight proteinuria, hypercalciuria, aminoaciduria and hypophosphataemia. Because of its rather rare occurrence, Dent's disease is often diagnosed as idiopathichypercalciuria, i.e., excess calcium in urine with undetermined causes.[citation needed]
^Mayo Clinic, Division of Nephrology and Hypertension, Mineral Metabolism and Stone Disease 2007-03-05 at the Wayback Machine
^S. Karger AG, Basel, Truncating Mutations in the Chloride/Proton ClC-5 Antiporter Gene in Seven Jewish Israeli Families with Dent’s 1 Disease
^ ab"Dent disease". National Center For Advancing Translational Sciences. Retrieved 4 July 2021.
^ abWrong OM; Norden AGW; Feest TG (1994). "Dent's disease; a familial proximal renal tubular syndrome with low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, metabolic bone disease, progressive kidney failure and a marked male predominance". Quarterly Journal of Medicine. 87 (8): 473–493. Archived from the original on 2012-07-14.
^Burgess HK, Jayawardene SA, Velasco N (July 2001). "Dent's disease: can we slow its progression?". Nephrol. Dial. Transplant. 16 (7): 1512–3. doi:10.1093/ndt/16.7.1512. PMID 11427657.
^Fisher SE, van Bakel I, Lloyd SE, Pearce SH, Thakker RV, Craig IW (October 1995). "Cloning and characterization of CLCN5, the human kidney chloride channel gene implicated in Dent disease (an X-linked hereditary nephrolithiasis)". Genomics. 29 (3): 598–606. doi:10.1006/geno.1995.9960. hdl:11858/00-001M-0000-0012-CC06-6. PMID 8575751.
^Jentsch TJ, Friedrich T, Schriever A, Yamada H (May 1999). . Pflügers Arch. 437 (6): 783–95. doi:10.1007/s004240050847. PMID 10370055. S2CID 2602342. Archived from the original on 2001-03-18. Retrieved 2009-12-08.
^Yamamoto K, Cox JP, Friedrich T, et al. (August 2000). "Characterization of renal chloride channel (CLCN5) mutations in Dent's disease". J. Am. Soc. Nephrol. 11 (8): 1460–8. doi:10.1681/ASN.V1181460. PMID 10906159.
^Hoopes RR, Shrimpton AE, Knohl SJ, et al. (February 2005). "Dent Disease with mutations in OCRL1". Am. J. Hum. Genet. 76 (2): 260–7. doi:10.1086/427887. PMC1196371. PMID 15627218.
^Loffing J (November 2004). "Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in the puzzle". J. Am. Soc. Nephrol. 15 (11): 2948–50. doi:10.1097/01.ASN.0000146568.82353.04. PMID 15504949.
^Raja KA, Schurman S, D'mello RG, et al. (December 2002). "Responsiveness of hypercalciuria to thiazide in Dent's disease". J. Am. Soc. Nephrol. 13 (12): 2938–44. doi:10.1097/01.ASN.0000036869.82685.F6. PMID 12444212.
^Cebotaru V, Kaul S, Devuyst O, et al. (August 2005). "High citrate diet delays progression of renal insufficiency in the ClC-5 knockout mouse model of Dent's disease". Kidney Int. 68 (2): 642–52. doi:10.1111/j.1523-1755.2005.00442.x. PMID 16014041.
dent, disease, dent, disease, rare, linked, recessive, inherited, condition, that, affects, proximal, renal, tubules, kidney, cause, fanconi, syndrome, characterized, tubular, proteinuria, excess, calcium, urine, formation, calcium, kidney, stones, nephrocalci. Dent s disease or Dent disease is a rare X linked recessive inherited condition that affects the proximal renal tubules 1 of the kidney It is one cause of Fanconi syndrome and is characterized by tubular proteinuria excess calcium in the urine formation of calcium kidney stones nephrocalcinosis and chronic kidney failure Dent s diseaseNephron of the kidney without juxtaglomerular apparatusSpecialtyUrology Named afterCharles Enrique Dent Dent s disease is often used to describe an entire group of familial disorders including X linked recessive nephrolithiasis with kidney failure X linked recessive hypophosphatemic rickets and both Japanese and idiopathic low molecular weight proteinuria 2 About 60 of patients have mutations in the CLCN5 gene Dent 1 which encodes a kidney specific chloride proton antiporter and 15 of patients have mutations in the OCRL1 gene Dent 2 3 Contents 1 Signs and symptoms 2 Genetics 2 1 Dent disease 1 2 2 Dent disease 2 3 Diagnosis 4 Treatment 5 History 6 References 7 External linksSigns and symptoms editDent s disease often produces the following signs and symptoms 4 Extreme thirst combined with dehydration which leads to frequent urination Nephrolithiasis kidney stones Hypercalciuria high urine calcium gt 300 mg d or gt 4 mg kg per d with normal levels blood serum calcium Aminoaciduria amino acids in urine Phosphaturia phosphate in urine Glycosuria glucose in urine Kaliuresis potassium in urine Hyperuricosuria excessive amounts of uric acid in the urine Impaired urinary acidification RicketsIn a study of 25 patients with Dent s disease 5 9 of 15 men and one of 10 women had end stage kidney disease by the age of 47 6 Genetics edit nbsp X linked recessive inheritance nbsp Three dimensional homology model of human CLC 5 based on the structure of ClC ec1 7 showing the locations of each mutated residueDent disease 1 edit Dent s disease is a X linked recessive disorder The males are prone to manifesting symptoms in early adulthood with symptoms of calculi rickets or even with kidney failure in more severe cases 4 In humans gene CLCN5 is located on chromosome Xp11 22 and has a 2238 bp coding sequence that consists of 11 exons that span 25 to 30 kb of genomic DNA and encode a 746 amino acid protein 7 CLCN5 belongs to the family of voltage gated chloride channel genes CLCN1 CLCN7 CLCKa and CLCKb that have about 12 transmembrane domains These chloride channels have an important role in the control of membrane excitability transepithelial transport and possibly cell volume 8 The mechanisms by which CLC 5 dysfunction results in hypercalciuria and the other features of Dent s disease remain to be elucidated The identification of additional CLCN5 mutations may help in these studies 9 Dent disease 2 edit Dent disease 2 nephrolithiasis type 2 is associated with the OCRL gene 10 11 Both Lowe syndrome oculocerebrorenal syndrome and Dent disease can be caused by truncating or missense mutations in OCRL Diagnosis editDiagnosis is based on genetic study of CLCN5 gene citation needed Treatment editAs of today no agreed upon treatment of Dent s disease is known and no therapy has been formally accepted Most treatment measures are supportive in nature Thiazide diuretics i e hydrochlorothiazide have been used with success in reducing the calcium output in urine but they are also known to cause hypokalemia In rats with diabetes insipidus thiazide diuretics inhibit the NaCl cotransporter in the renal distal convoluted tubule leading indirectly to less water and solutes being delivered to the distal tubule 12 The impairment of Na transport in the distal convoluted tubule induces natriuresis and water loss while increasing the reabsorption of calcium in this segment in a manner unrelated to sodium transport Amiloride also increases distal tubular calcium reabsorption and has been used as a therapy for idiopathic hypercalciuria A combination of 25 mg of chlorthalidone plus 5 mg of amiloride daily led to a substantial reduction in urine calcium in Dent s patients but urine pH was significantly higher in patients with Dent s disease than in those with idiopathic hypercalciuria P lt 0 03 and supersaturation for uric acid was consequently lower P lt 0 03 13 For patients with osteomalacia vitamin D or derivatives have been employed apparently with success Some lab tests on mice with CLC 5 related tubular damage showed a high citrate diet preserved kidney function and delayed progress of kidney disease 14 History editDent s disease was first described by Charles Enrique Dent and M Friedman in 1964 when they reported two unrelated British boys with rickets associated with renal tubular damage characterized by hypercalciuria hyperphosphaturia proteinuria and aminoaciduria 15 This set of symptoms was not given a name until 30 years later when the nephrologist Oliver Wrong more fully described the disease 5 Wrong had studied with Dent and chose to name the disease after his mentor 16 Dent s disease is a genetic disorder caused by mutations in the gene CLCN5 which encodes a kidney specific voltage gated chloride channel a 746 amino acid protein CLC 5 with 12 to 13 transmembrane domains It manifests itself through low molecular weight proteinuria hypercalciuria aminoaciduria and hypophosphataemia Because of its rather rare occurrence Dent s disease is often diagnosed as idiopathic hypercalciuria i e excess calcium in urine with undetermined causes citation needed References edit Dent disease at Dorland s Medical Dictionary Mayo Clinic Division of Nephrology and Hypertension Mineral Metabolism and Stone Disease Archived 2007 03 05 at the Wayback Machine S Karger AG Basel Truncating Mutations in the Chloride Proton ClC 5 Antiporter Gene in Seven Jewish Israeli Families with Dent s 1 Disease a b Dent disease National Center For Advancing Translational Sciences Retrieved 4 July 2021 a b Wrong OM Norden AGW Feest TG 1994 Dent s disease a familial proximal renal tubular syndrome with low molecular weight proteinuria hypercalciuria nephrocalcinosis metabolic bone disease progressive kidney failure and a marked male predominance Quarterly Journal of Medicine 87 8 473 493 Archived from the original on 2012 07 14 Burgess HK Jayawardene SA Velasco N July 2001 Dent s disease can we slow its progression Nephrol Dial Transplant 16 7 1512 3 doi 10 1093 ndt 16 7 1512 PMID 11427657 Fisher SE van Bakel I Lloyd SE Pearce SH Thakker RV Craig IW October 1995 Cloning and characterization of CLCN5 the human kidney chloride channel gene implicated in Dent disease an X linked hereditary nephrolithiasis Genomics 29 3 598 606 doi 10 1006 geno 1995 9960 hdl 11858 00 001M 0000 0012 CC06 6 PMID 8575751 Jentsch TJ Friedrich T Schriever A Yamada H May 1999 The CLC chloride channel family Pflugers Arch 437 6 783 95 doi 10 1007 s004240050847 PMID 10370055 S2CID 2602342 Archived from the original on 2001 03 18 Retrieved 2009 12 08 Yamamoto K Cox JP Friedrich T et al August 2000 Characterization of renal chloride channel CLCN5 mutations in Dent s disease J Am Soc Nephrol 11 8 1460 8 doi 10 1681 ASN V1181460 PMID 10906159 Online Mendelian Inheritance in Man OMIM 300555 Hoopes RR Shrimpton AE Knohl SJ et al February 2005 Dent Disease with mutations in OCRL1 Am J Hum Genet 76 2 260 7 doi 10 1086 427887 PMC 1196371 PMID 15627218 Loffing J November 2004 Paradoxical antidiuretic effect of thiazides in diabetes insipidus another piece in the puzzle J Am Soc Nephrol 15 11 2948 50 doi 10 1097 01 ASN 0000146568 82353 04 PMID 15504949 Raja KA Schurman S D mello RG et al December 2002 Responsiveness of hypercalciuria to thiazide in Dent s disease J Am Soc Nephrol 13 12 2938 44 doi 10 1097 01 ASN 0000036869 82685 F6 PMID 12444212 Cebotaru V Kaul S Devuyst O et al August 2005 High citrate diet delays progression of renal insufficiency in the ClC 5 knockout mouse model of Dent s disease Kidney Int 68 2 642 52 doi 10 1111 j 1523 1755 2005 00442 x PMID 16014041 Dent CE Friedman M 1964 Hypercalcuric Rickets Associated with Renal Tubular Damage Arch Dis Child 39 205 240 9 doi 10 1136 adc 39 205 240 PMC 2019188 PMID 14169453 Professor Oliver Wrong 1924 2012 permanent dead link External links editGenetic Hypercalciuria Dent disease on Orphanet Retrieved from https en wikipedia org w index php title Dent 27s disease amp oldid 1185208555, wikipedia, wiki, book, books, library,
