合并肾囊性病变儿童1型Dent病1例报告
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摘要
目的探讨儿童Dent病1型合并肾囊性病变的可能发病原因。方法回顾1例16岁男性肾囊性病变患儿的临床资料,并复习相关文献。结果患儿发现蛋白尿、双肾多发囊肿4年,肾功能异常3年,临床主要表现为肾病水平的小分子蛋白尿、高钙尿症、肾功能异常并进行性加重、双肾多发囊肿、低钾血症。肾脏病理为局灶节段性肾小球硬化伴肾小管间质损伤。CLCN 5基因突变分析示c. 1975 delC(p.R 659 Gfs*7),NPHP相关基因未见突变。诊断为Dent病1型合并肾囊性病变、慢性肾脏病。结论 Dent病1型合并肾囊性病变较为罕见,其确切机制尚不清楚。
Objective To explore the possible mechanism in childhood Dent disease combined with renal cystic disease.Methods Clinical data were collected and analyzed from 1 childhood Dent disease cases combined with renal cystic disease.Results The case presented with nephrotic level low-molecular weight proteinuria, hypercalciuria, progressive renal failure,multiple cysts in both kidney and hypopotassemia. Renal biopsy showed focal segmental glomerulosclerosis combined with tubulointerstitial damage. Gene mutation analysis showed a hemizygous mutation(c. 1975 delC, p.R 659 Gfs* 7) in CLCN5 gene,and no positive result on nephronophthisis related genes was found. Conclusions Dent disease combined with renal cystic disease is a rare phenomenon, with reasons unknown.
Objective To explore the possible mechanism in childhood Dent disease combined with renal cystic disease.Methods Clinical data were collected and analyzed from 1 childhood Dent disease cases combined with renal cystic disease.Results The case presented with nephrotic level low-molecular weight proteinuria, hypercalciuria, progressive renal failure,multiple cysts in both kidney and hypopotassemia. Renal biopsy showed focal segmental glomerulosclerosis combined with tubulointerstitial damage. Gene mutation analysis showed a hemizygous mutation(c. 1975 delC, p.R 659 Gfs* 7) in CLCN5 gene,and no positive result on nephronophthisis related genes was found. Conclusions Dent disease combined with renal cystic disease is a rare phenomenon, with reasons unknown.
引文
[1]Utsch B,B?kenkamp A,Benz MR,et al.Novel OCRL1mutations in patients with the phenotype of Dent disease[J].Am J Kidney Dis,2006,48(6):942 e1-14.
[2]Grand T,L'Hoste S,Mordasini D,et al.Heterogeneity in the processing of CLCN5 mutants related to Dent disease[J].Hum Mutat,2011,32(4):476-483.
[3]Devuyst O.Dent's disease:chloride-proton exchange controls proximal tubule endocytosis[J].Nephrol Dial Transplant,2010,25(12):3832-3835.
[4]Cho HY,Lee BH,Choi HJ,et al.Renal manifestations of Dent disease and Lowe syndrome[J].Pediatr Nephrol(Berlin,Germany),2008,23(2):243-249.
[5]Annigeri RA,Rajagopalan R.Hypophosphatemic rickets due to Dent's disease:a case report and review of literature[J].Indian J Nephrol,2009,19(4):163-166.
[6]Slaats GG,Lilien MR,Giles RH.Nephronophthisis:should we target cysts or fibrosis?[J].Pediatr Nephrol,2016,31(4):545-554.
[7]Bisceglia M,Galliani CA,Senger C,et al.Renal cystic diseases:a review[J].Adv Anat Pathol,2006,13(1):26-56.
[8]Kagan KO,Dufke A,Gembruch U.Renal cystic disease and associated ciliopathies[J].Curr Opin Obstet Gynecol,2017,29(2):85-94.
[9]Sobiak J,Resztak M,Ostalska-Nowicka D,et al.Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters[J].Eur J Pharm Sci,2015,77:189-196.
[10]Torres VE,Young WF Jr,Offord KP,et al.Association of hypokalemia,aldosteronism,and renal cysts[J].N Engl JMed,1990,322(6):345-351.
[11]Novello M,Catena C,Nadalini E,et al.Renal cysts and hypokalemia in primary aldosteronism:results of long-term follow-up after treatment[J].J Hypertens,2007,25(7):1443-1450.
[12]Watanabe T,Tajima T.Renal cysts and nephrocalcinosis in a patient with Bartter syndrome type III[J].Pediatr Nephrol,2005,20(5):676-678.
[13]Igarashi T,Shibuya K,Kamoshita S,et al.Renal cyst formation as a complication of primary distal renal tubular acidosis[J].Nephron,1991,59(1):75-79.
[14]刘美娜,陈述枚,卢亚亚,等.小儿囊肿性肾病47例[J].实用儿科临床杂志,2007,22(17):1317-1318.
[15]Simms RJ,Hynes AM,Eley L,et al.Nephronophthisis:a genetically diverse ciliopathy[J].Int J Nephrol,2011,2011:527137.
[16]Wolf MT.Nephronophthisis and related syndromes[J].Curr Opin Pediatr,2015,27(2):201-211.
[17]Adams NA,Awadein A,Toma HS.The retinal ciliopathies[J].Ophthalmic Genet,2007,28(3):113-125.
[18]Arts HH,Knoers NV.Current insights into renal ciliopathies:what can genetics teach us?[J].Pediatr Nephrol,2013,28(6):863-874.
[19]Coon BG,Hernandez V,Madhivanan K,et al.The Lowe syndrome protein OCRL1 is involved in primary cilia assembly[J].Hum Mol Genet,2012,21(8):1835-1847.
[20]何国华,张宏文,王芳,等.儿童Dent病4例的肾脏病理改变分析[J].中华实用儿科临床杂志,2017,32(5):387-389.
[21]Wrong OM,Norden AG,Feest TG.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[J].QJM,1994,87(8):473-493.
[22]Thakker RV.Pathogenesis of Dent's disease and related syndromes of X-linked nephrolithiasis[J].Kidney Int,2000,57(3):787-793.
[23]Claverie-Martin F,Ramos-Trujillo E,Garcia-Nieto V.Dent's disease:clinical features and molecular basis[J].Pediatr Nephrol,2011,26(5):693-704.
[24]Simms RJ,Hynes AM,Eley L,et al.Modelling a ciliopathy:Ahi1 knockdown in model systems reveals an essential role in brain,retinal,and renal development[J].Cell Mol Life Sci,2012,69(6):993-1009.
[25]Wang J,Deretic D.Molecular complexes that direct rhodopsin transport to primary cilia[J].Prog Retin Eye Res,2014,38:1-19.
[26]Keller LC,Geimer S,Romijn E,et al.Molecular architecture of the centriole proteome:the conserved WD40 domain protein POC1 is required for centriole duplication and length control[J].Mol Biol Cell,2009,20(4):1150-1166.
[27]Holder M,Bald M,Leichter HE,et al.Dent disease with compound heterozygous mutations leading to severe chronic renal failure in a female patient[J].Pediatr Nephrol,2004,19(1):122.
[28]Simms RJ,Sayer JA.Juvenile nephronophthisis on MRI--a potential case of Joubert syndrome?[J].Pediatr Radiol,2010,40(9):1581.
[29]仇丽茹,周建华.82例儿童慢性肾功能衰竭临床分析[J].临床儿科杂志,2004,22(12):789-791.
[30]张宏文,苏白鸽,王芳,等.Dent病合并肾衰竭2例报告并文献复习[J].临床儿科杂志,2018,36(6):416-419.
[31]Szczepanska M,Zaniew M,Recker F,et al.Dent disease in children:diagnostic and therapeutic considerations[J].Clin Nephrol,2015,84(4):222-230.
[2]Grand T,L'Hoste S,Mordasini D,et al.Heterogeneity in the processing of CLCN5 mutants related to Dent disease[J].Hum Mutat,2011,32(4):476-483.
[3]Devuyst O.Dent's disease:chloride-proton exchange controls proximal tubule endocytosis[J].Nephrol Dial Transplant,2010,25(12):3832-3835.
[4]Cho HY,Lee BH,Choi HJ,et al.Renal manifestations of Dent disease and Lowe syndrome[J].Pediatr Nephrol(Berlin,Germany),2008,23(2):243-249.
[5]Annigeri RA,Rajagopalan R.Hypophosphatemic rickets due to Dent's disease:a case report and review of literature[J].Indian J Nephrol,2009,19(4):163-166.
[6]Slaats GG,Lilien MR,Giles RH.Nephronophthisis:should we target cysts or fibrosis?[J].Pediatr Nephrol,2016,31(4):545-554.
[7]Bisceglia M,Galliani CA,Senger C,et al.Renal cystic diseases:a review[J].Adv Anat Pathol,2006,13(1):26-56.
[8]Kagan KO,Dufke A,Gembruch U.Renal cystic disease and associated ciliopathies[J].Curr Opin Obstet Gynecol,2017,29(2):85-94.
[9]Sobiak J,Resztak M,Ostalska-Nowicka D,et al.Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters[J].Eur J Pharm Sci,2015,77:189-196.
[10]Torres VE,Young WF Jr,Offord KP,et al.Association of hypokalemia,aldosteronism,and renal cysts[J].N Engl JMed,1990,322(6):345-351.
[11]Novello M,Catena C,Nadalini E,et al.Renal cysts and hypokalemia in primary aldosteronism:results of long-term follow-up after treatment[J].J Hypertens,2007,25(7):1443-1450.
[12]Watanabe T,Tajima T.Renal cysts and nephrocalcinosis in a patient with Bartter syndrome type III[J].Pediatr Nephrol,2005,20(5):676-678.
[13]Igarashi T,Shibuya K,Kamoshita S,et al.Renal cyst formation as a complication of primary distal renal tubular acidosis[J].Nephron,1991,59(1):75-79.
[14]刘美娜,陈述枚,卢亚亚,等.小儿囊肿性肾病47例[J].实用儿科临床杂志,2007,22(17):1317-1318.
[15]Simms RJ,Hynes AM,Eley L,et al.Nephronophthisis:a genetically diverse ciliopathy[J].Int J Nephrol,2011,2011:527137.
[16]Wolf MT.Nephronophthisis and related syndromes[J].Curr Opin Pediatr,2015,27(2):201-211.
[17]Adams NA,Awadein A,Toma HS.The retinal ciliopathies[J].Ophthalmic Genet,2007,28(3):113-125.
[18]Arts HH,Knoers NV.Current insights into renal ciliopathies:what can genetics teach us?[J].Pediatr Nephrol,2013,28(6):863-874.
[19]Coon BG,Hernandez V,Madhivanan K,et al.The Lowe syndrome protein OCRL1 is involved in primary cilia assembly[J].Hum Mol Genet,2012,21(8):1835-1847.
[20]何国华,张宏文,王芳,等.儿童Dent病4例的肾脏病理改变分析[J].中华实用儿科临床杂志,2017,32(5):387-389.
[21]Wrong OM,Norden AG,Feest TG.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[J].QJM,1994,87(8):473-493.
[22]Thakker RV.Pathogenesis of Dent's disease and related syndromes of X-linked nephrolithiasis[J].Kidney Int,2000,57(3):787-793.
[23]Claverie-Martin F,Ramos-Trujillo E,Garcia-Nieto V.Dent's disease:clinical features and molecular basis[J].Pediatr Nephrol,2011,26(5):693-704.
[24]Simms RJ,Hynes AM,Eley L,et al.Modelling a ciliopathy:Ahi1 knockdown in model systems reveals an essential role in brain,retinal,and renal development[J].Cell Mol Life Sci,2012,69(6):993-1009.
[25]Wang J,Deretic D.Molecular complexes that direct rhodopsin transport to primary cilia[J].Prog Retin Eye Res,2014,38:1-19.
[26]Keller LC,Geimer S,Romijn E,et al.Molecular architecture of the centriole proteome:the conserved WD40 domain protein POC1 is required for centriole duplication and length control[J].Mol Biol Cell,2009,20(4):1150-1166.
[27]Holder M,Bald M,Leichter HE,et al.Dent disease with compound heterozygous mutations leading to severe chronic renal failure in a female patient[J].Pediatr Nephrol,2004,19(1):122.
[28]Simms RJ,Sayer JA.Juvenile nephronophthisis on MRI--a potential case of Joubert syndrome?[J].Pediatr Radiol,2010,40(9):1581.
[29]仇丽茹,周建华.82例儿童慢性肾功能衰竭临床分析[J].临床儿科杂志,2004,22(12):789-791.
[30]张宏文,苏白鸽,王芳,等.Dent病合并肾衰竭2例报告并文献复习[J].临床儿科杂志,2018,36(6):416-419.
[31]Szczepanska M,Zaniew M,Recker F,et al.Dent disease in children:diagnostic and therapeutic considerations[J].Clin Nephrol,2015,84(4):222-230.