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Renal Mitochondrial Cytopathies

By Francesco Emma, Giovanni Montini, Leonardo Salviati and Carlo Dionisi-Vici

Abstract

Renal diseases in mitochondrial cytopathies are a group of rare diseases that are characterized by frequent multisystemic involvement and extreme variability of phenotype. Most frequently patients present a tubular defect that is consistent with complete De Toni-Debré-Fanconi syndrome in most severe forms. More rarely, patients present with chronic tubulointerstitial nephritis, cystic renal diseases, or primary glomerular involvement. In recent years, two clearly defined entities, namely 3243 A > G tRNALEU mutations and coenzyme Q10 biosynthesis defects, have been described. The latter group is particularly important because it represents the only treatable renal mitochondrial defect. In this paper, the physiopathologic bases of mitochondrial cytopathies, the diagnostic approaches, and main characteristics of related renal diseases are summarized

Topics: Review Article
Publisher: SAGE-Hindawi Access to Research
OAI identifier: oai:pubmedcentral.nih.gov:3146993
Provided by: PubMed Central

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Citations

  1. (2004). A boy with mitochondrial disease: asymptomatic proteinuria without neuromyopathy,”
  2. (1998). A case of mitochondrialcytopathywithatypicalpointmutationforMELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation,”
  3. (1996). A case of Pearson syndrome associated with multiple renal cysts,”
  4. (2006). A mutation in parahydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency,”
  5. (1994). a n dV .D ’ A g a t i ,“ M i t o c h o n d r i a lD N Ad e l e t i o n :ac a u s eo f chronic tubulointerstitial nephropathy,”
  6. (2009). A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease,”
  7. (2009). A novel mutation of the RRM2B gene in an infant with early fatal encephalomyopathy, central hypomyelination,
  8. (2005). a r i s o n i ,M .P .M a d a i o ,M .E r a s o ,D .L .G a s s e r ,a n dP .J . Nelson, “The kd/kd mouse is a model of collapsing glomerulopathy,”
  9. (1971). An inherited kidney disease of miceresemblinghumannephronophthisis,”JournalofMedical
  10. (2007). Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation,”JournalofMedicalGenetics,vol.44,no.12,pp.784– 786,
  11. (2005). As ¸an et al., “Focal segmental glomerulosclerosis associated with mitochondrial cytopathy: report of two cases with special emphasis on podocytes,”
  12. (2001). C.Y.Tzen,J.D.Tsai,T.Y.Wuetal.,“Tubulointerstitialnephritis associated with a novel mitochondrial point mutation,”
  13. (2011). Chaki et al., “COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness,”
  14. (2001). Clinical and pathologic features of focal segmental glomerulosclerosis with mitochondrial tRNALeu(UUR)genemutation,”KidneyInternational,vol.59,
  15. (2009). Coenzyme Q deficiency triggers mitochondria degradation by mitophagy,”
  16. (2008). Coenzyme Q10 supplementation rescues renal disease in Pdss2 kd/kd mice with mutations in prenyl diphosphate synthase subunit 2,”
  17. (2007). COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement,”
  18. (2007). D .R.Thorburn,D .M.T urnbull,andR.W .T aylor , “Biochemical assays of respiratory chain complex activity,”
  19. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies,”
  20. (1989). Detection of “deleted” mitochondrial genomes in cytochromeoxidase-deficient muscle fibers of a patient with Kearns—Sayre syndrome,”
  21. (2008). Early coenzyme Q10 supplementation in primary coenzyme Q10 deficiency,”10
  22. (2004). Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein,”
  23. (1996). Fetal polycystic kidney disease associated with glutaric aciduria type II: an inborn error of energy metabolism,”
  24. (2000). Focal segmental glomerulosclerosis associated with mitochondrial cytopathy,” Kidney International,vol.58,no.5,pp.1851–1858,
  25. (2005). Four-month-old infant with focal segmental glomerulosclerosis and mitochondrial DNA deletion,”
  26. (2002). GRACILE syndrome, a lethal metabolic disorder with iron overload, is caused byInternational
  27. (2003). Guercin et al., “Mutations in COX10 result in a defect in mitochondrial heme A biosynthesis and account for multiple, early-onset clinical phenotypes associated with isolated
  28. (2006). H a l l m a n ,M .P e n g ,R .M e a d e ,W .W .H a n c o c k
  29. (2003). h a r m a ,A .A .P e r s z y k ,D .M a r a n g i ,C .M o n t e i r o ,a n dS . Raja, “Lethal neonatal carnitine palmitoyltransferase II defi-ciency: an unusual presentation of a rare disorder,”
  30. (1999). Hair and skin disorders as signs of mitochondrial disease,”
  31. (2005). hCOX18 and hCOX19: two human genes involved in cytochrome c oxidase assembly,”
  32. (1999). Hereditary glomerulopathy associated with a mitochondrial tRNA(Leu) gene mutation,”
  33. (2006). Ifosfamide-induced nephrotoxicity: mechanism and prevention,”
  34. (2005). Infantile encephalomyopathy and nephropathy with
  35. (2004). Isolation and functional expression of human COQ2, a gene encoding a polyprenyl transferase involved in the synthesis of
  36. (2008). L´ opez et al., “ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency,”
  37. (2006). Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphote synthase subunit 2 (PDSS2) mutations,”
  38. (1995). Lethal neonatal deficiency of carnitine palmitoyltransferase II associated with dysgenesis of the brain andkidneys,”JournalofPediatrics,vol.127,no.3,pp.414–420,
  39. (1991). M o r a e s ,S .S h a n s k e ,H .J .T r i t s c h l e re ta l .
  40. (2002). M.Hirano,K.Konishi,N.Arataetal.,“Renalcomplicationsin a patient with A-to-G mutation of mitochondrial DNA at the 3243 position of leucine tRNA,”
  41. (2001). Mitochondrial cytopathy presenting withfocalsegmentalglomerulosclerosis,hypoparathyroidism, sensorineural deafness, and progressive neurological disease,”
  42. (2007). Mitochondrial disease—its impact, etiology, and pathology,”
  43. (2008). Mitochondrial disorders in the nervous system,”
  44. (2007). Mitochondrial DNA deletion in a girl with Fanconi’s syndrome,”
  45. (2009). Mitochondrial encephalomyopathies and related syndromes: brief review,”
  46. (1996). Mitochondrial encephalomyopathies preceded by de-Toni-Debr´ e-Fanconi syndrome or focal segmental glomerulosclerosis,”
  47. (2001). Mitochondrial medicine—molecular pathology of defective oxidative phosphorylation,”
  48. (1984). Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study,” Virchows Archive B: Cell Pathology Including Molecular Pathology,
  49. (2003). Mitochondrial respiratorychain diseases,” New England
  50. (2005). Mitochondrial tRNALeu(UUR) mutation in a patient with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis,”
  51. (2004). Mitochondriopathies,”
  52. (1996). Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: as t u d yo f5 6p a t i e n t s ,
  53. (2009). Multisystem manifestations of mitochondrial disorders,”
  54. (1989). Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy,”
  55. (2004). Mutant prenyltransferaselike mitochondrial protein (PLMP) and mitochondrial abnormalities in kd/kd mice,”
  56. (1997). Mutation in mitochondrial tRNA(Leu(UUR)) gene associated with progressive kidney disease,”
  57. (2011). Mutations in the mitochondrial Seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy andalkalosis,HUPRAsyndrome,”AmericanJournalofHuman
  58. (2003). Nephrotoxicity and the proximal tubule. Insights from cadmium,”
  59. (2010). New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria,”
  60. (1978). Nutritional inhibition of genetically determined renal disease and autoimmunity with prolongation of life in kdkd mice,”
  61. (2008). o l l e t ,A .D e l a h o d d e ,V .S e r r ee ta l .
  62. (1995). o t i g ,F .G o u t i ` eres, P. Niaudet et al., “Deletion of mitochondrial DNA in a patient with chronic tubulointerstitial nephritis,”
  63. (2001). O.Musumeci,A.Naini,A.E.Slonimetal.,“Familialcerebellar ataxia with muscle coenzyme Q10 deficiency,”
  64. (1992). Partial deficiency of cytochrome c oxidase with isolated proximal renal tubular acidosis and hypercalciuria,”
  65. (1996). Pearson’s syndrome presenting
  66. (1998). Persistent hypocitrullinaemia as a marker for mtDNA
  67. (2008). Physicochemical and pharmacokinetic characterization of water-soluble Coenzyme Q(10) formulations,”
  68. (2007). Prenyldiphosphate synthase, subunit 1 (PDSS1) and OH-benzoate polyprenyltransferase (COQ2) mutations in ubiquinone deficiency and oxidativephosphorylationdisorders,”JournalofClinicalInvestigation,
  69. (2000). Quinoneresponsive multiple respiratory-chain dysfunction due to widespread coenzyme
  70. (2010). Reactive oxygen species, oxidative stress, and cell death correlate with level of
  71. (1999). Recognition andmanagementoffattyacidoxidationdefects:aseriesof107 patients,”
  72. (1999). Renal complications in patients with diabetes mellitus associated with an A to G mutation of mitochondrial DNA at the 3243 position of leucine tRNA,”
  73. (2000). Renal Fanconi syndrome: first sign of partial respiratory chain complexIVdeficiency,”PediatricNephrology,vol.14,no.6,pp. 495–498,
  74. (2005). Renal pathology in children with mitochondrial diseases,”
  75. (1990). Renal tubular involvement mimicking Bartter syndrome in a patient with Kearns—Sayre syndrome,”
  76. (2005). Respiratory chain deficiency presenting as congenital nephrotic syndrome,”
  77. (2008). Respiratory chain dysfunction and oxidative stress correlate with severity of primary
  78. (1992). Saudubray et al., “Brief report: renal tubular acidosis in carnitine palmitoyltransferase type 1 deficiency,”
  79. (2001). Severe hypomagnesemia and hypoparathyroidism in KearnsSayre syndrome,”
  80. (2007). SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness,”
  81. (1997). The kidney in mitochondrial cytopathies,”
  82. (2003). The spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation,”
  83. (2010). Treatment of CoQ(10) deficient fibroblasts with ubiquinone,
  84. (2008). Trevisson et al., “Functional characterization of human COQ4, a gene required for Coenzyme Q10 biosynthesis,”
  85. (2007). Trevisson et al., “Missense mutation of the COQ2 gene causes defects of bioenergetics and de novo pyrimidine synthesis,”
  86. (2005). Tubulointerstitial nephritis and fanconi syndrome in primary biliary cirrhosis,”
  87. (2002). Tyrosinaemia type I and apoptosis of hepatocytes and renal tubular cells,”