Pediatric Nephrology

, Volume 20, Issue 9, pp 1299–1305 | Cite as

Renal pathology in children with mitochondrial diseases

  • Elena Martín-Hernández
  • M. Teresa García-Silva
  • Julia Vara
  • Yolanda Campos
  • Ana Cabello
  • Rafael Muley
  • Pilar del Hoyo
  • Miguel Angel Martín
  • Joaquín Arenas
Original Article


We studied renal involvement in 42 children with mitochondrial diseases (MDs). The diagnosis of MD was established by morphological, biochemical, and molecular genetic criteria. Renal disease was considered when patients had renal failure, nephrotic syndrome, Fanconi’s syndrome or any symptomatic renal alteration. Mild tubular disorder was established if they had abnormal laboratory findings with no apparent clinical symptom. Renal involvement was found in 21 children (50%), of whom 8 had an apparent clinical picture and 13 a mild tubular disorder. Five patients with renal disease showed Debré–Toni–Fanconi’s syndrome, 2 of them with decreased glomerular filtration rate (GFR). One case had nephrotic syndrome, another one presented decreased GFR, and the last one had a neurogenic bladder and bilateral hydronephrosis. Patients with mild renal disease showed tubular dysfunction with normal GFR. Renal involvement is frequent and present in about half of the children with MD. Thus, studies for evaluating kidney function should be performed on children with MD. Conversely, patients with tubulopathy of unknown origin or progressive renal disease should be investigated for the existence of MD, especially if associated with involvement of other organs or tissues. Southern blot analysis to search for large-scale mitochondrial DNA (mtDNA) rearrangements should be performed for patients with MD and kidney involvement.


Mitochondrial Respiratory chain OXPHOS Renal involvement Kearns-Sayre syndrome Pearson syndrome 



We thank Dr de Meirleir and colleagues for their collaboration in the studies of case 4.


  1. 1.
    Bernier FP, Boneh A, Dennet X, Chow CW, Cleary MA, Thorburn DR (2002) Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 59:1406–1411PubMedGoogle Scholar
  2. 2.
    Munnich A, Rötig A, Chretien D, Cornier V, Bourgeron T, Bonnefont JP, Saudubray JM, Rustin P (1996) Clinical presentation of mitochondrial disorders in childhood. J Inherit Metab Dis 19:521–527PubMedGoogle Scholar
  3. 3.
    García-Silva MT (2001) Diagnóstico clínico de las enfermedades de la cadena respiratoria y fosforilación oxidativa. In: Sanjurjo P, Baldellou A (eds) Diagnóstico y tratamiento de las enfermedades metabólicas hereditarias. Ergon, Madrid, pp 389–403Google Scholar
  4. 4.
    Niaudet P (1998) Mitochondrial disorders and the kidney. Arch Dis Child 78:387–390PubMedGoogle Scholar
  5. 5.
    Rötig A (2003) Renal disease and mitochondrial genetics. J Nephrol 16:286–292CrossRefPubMedGoogle Scholar
  6. 6.
    Neiberger RE, George JC, Perkins LA, Theriaque DW, Hutson AD, Stacpoole PW (2002) Renal manifestations of congenital lactic acidosis. Am J Kidney Dis 39:12–23PubMedGoogle Scholar
  7. 7.
    Singh PJ, Santella RN, Zawada ET (1996) Mitochondrial genome mutations and kidney disease. Am J Kidney Dis 28:140–146PubMedGoogle Scholar
  8. 8.
    Lee YS, Yap HK, Barshop BA, Lee YS, Rajalingam S, Loke KY (2001) Mitochondrial tubulopathy: the many faces of mitochondrial disorders. Pediatr Nephrol 16:710–712CrossRefPubMedGoogle Scholar
  9. 9.
    Moulonguet Doleris L, Hill GS, Chedin P, Nochy D, Bellane-Chantelot C, Hanslik T, Bedrossian J, Caillat-Zucman S, Cahen-Varsaux J, Bariety J (2002) Focal segmental glomerulosclerosis associated with mitochondrial cytopathy. Kidney Int 58:1851–1858Google Scholar
  10. 10.
    Mochizuki H, Joh K, Kawame H, Imadachi A, Nozaki H, Ohashi T, Usui N, Eto Y, Kanetsuna Y, Aizawa S (1996) Mitochondrial encephalomyopathies preceded by de Toni–Debré–Fanconi syndrome or focal segmental glomerulosclerosis. Clin Nephrol 46:347–352PubMedGoogle Scholar
  11. 11.
    Kuwertz-Broking E, Koch HG, Marquardt T, Rossi R, Helmchen U, Muller-Hocker J, Harms E, Bulla M (2000) Renal Fanconi syndrome: first sign of partial respiratory chain complex IV deficiency. Pediatr Nephrol 14:495–498CrossRefPubMedGoogle Scholar
  12. 12.
    Tulinius NH, Oldfors A, Holme E, Larsson NG, Houshmand M, Fahleson P, Sigstrom L, Kristiansson B (1995) Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions. Eur J Pediatr 154:35–42CrossRefPubMedGoogle Scholar
  13. 13.
    Szabolcs MJ, Seigle R, Shanske S, Bonilla E, DiMauro S, D’Agati V (1994) Mitochondrial DNA deletion: a cause of chronic tubulointerstitial nephropathy. Kidney Int 45:1388–1396PubMedGoogle Scholar
  14. 14.
    Ogier H, Lombes A, Scholte HR, Poll-The BT, Fardeau M, Aicardi J, Vignes B, Niaudet P, Saudubray JM (1988) De Toni–Fanconi–Debré syndrome with Leigh syndrome revealing severe muscle cytochrome C oxidase deficiency. J Pediatr 112:734–739PubMedGoogle Scholar
  15. 15.
    Morris AAM, Taylor BW, Birch-Machin MA, Jackson MJ, Coulthard MG, Bindoff LA, Welch RJ, Howell N, Turnbull DM (1995) Neonatal Fanconi syndrome due to deficiency of complex III of the respiratory chain. Pediatr Nephrol 9:407–411CrossRefPubMedGoogle Scholar
  16. 16.
    Niaudet P, Heidet L, Munnich A, Schmitz J, Bouissou F, Gubler MC, Rötig A (1994) Deletion of the mitochondrial DNA in a case of the Toni–Debré–Fanconi syndrome and Pearson syndrome. Pediatr Nephrol 8:164–168CrossRefPubMedGoogle Scholar
  17. 17.
    Berio A, Piazzi A (2001) Kearns-Sayre syndrome associated with de Toni–Debre–Fanconi syndrome due to cytochrome C-oxidase (COX) deficiency. Panminerva Med 43:211–214PubMedGoogle Scholar
  18. 18.
    Van Biervliet JP, Bruinvis L, Ketting D, De Bree PK, Van der Heiden C, Wadman SK (1977) Hereditary mitochondrial myopathy with lactic acidosis, a de Toni–Fanconi–Debré syndrome and a defective respiratory chain in voluntary striated muscles. Pediatr Res 11:1088–1093PubMedGoogle Scholar
  19. 19.
    McShane MA, Hammans SR, Sweeney M, Holt IJ, Beattie TJ, Brett EM, Harding AE (1991) Pearson syndrome and mitochondrial encephalopathy in a patient with a deletion of the mtDNA. Am J Hum Genet 48:39–42Google Scholar
  20. 20.
    Zeviani M, Nonaka I, Bonilla E, Okino E, Moggio M, Jones S, DiMauro S (1985) Fatal infantile mitochondrial myopathy and renal dysfunction caused by cytochrome C oxidoreductase deficiency: immunological study of a new patient. Ann Neurol 17:414–417CrossRefPubMedGoogle Scholar
  21. 21.
    Majander A, Suomalainen A, Vettenrantta K, Sariola H, Perkkio M, Holmberg C, Pihko H (1991) Congenital hypoplastic anemia, diabetes, and severe renal tubular dysfunction associated with a mitochondrial DNA deletion. Pediatr Res 30:327–330Google Scholar
  22. 22.
    Sperl W, Ruttenbeek W, Tribels JMF, Sengers RCA, Stadhouders AM, Guggenbichler JP (1988) Mitochondrial myopathy with lactic acidemia, Fanconi–de Toni–Debré syndrome and a disturbed succinate-cytochrome C oxidoreductase activity. Eur J Pediatr 147:414–421Google Scholar
  23. 23.
    Hameed R, Raafat F, Ramani P, Gray G, Roper HP, Milfor DV (2001) Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease. Postgrad Med J 77:523–526CrossRefPubMedGoogle Scholar
  24. 24.
    Cheong HI, Chae JH, Kim JS, Park HW, Ha IS, Hwang YS, Lee HS, Choi Y 1999) Hereditary glomerulopathy associated with a mitochondrial tRNA (Leu) gene mutation. Pediatr Nephrol 13:477–480Google Scholar
  25. 25.
    Kurogouchi F, Oguchi T, Mawatari E, Yamaura S, Hora K, Takei M, Sekijima Y, Ikeda S, Kiyosawa K (1998) A case of mitochondrial cytopathy with a typical point mutation for MELAS, presenting with severe focal-segmental glomerulosclerosis as main clinical manifestation. Am J Nephrol 18:551–556CrossRefPubMedGoogle Scholar
  26. 26.
    Goto Y, Itami N, Kajii N, Tochimaru H, Endo M, Horai S (1990) Renal tubular involvement mimicking Bartter syndrome in a patient with Kearns-Sayre syndrome. J Pediatr 116:904–910PubMedGoogle Scholar
  27. 27.
    Tzen CY, Tsai JD, Wu TY, Chen BF, Chen ML, Lin SP, Chen SC (2001) Tubulointerstitial nephritis associated with a novel mitochondrial point mutation. Kidney Int 59:846–854CrossRefPubMedGoogle Scholar
  28. 28.
    Rötig A, Goutieres F, Niaudet P, Rustin P, Chretien D, Guest G, Mikol J, Gubler MC, Munnich A (1995) Deletion of mitochondrial DNA in a patient with chronic tubulointerstitial nephritis. J Pediatr 126:597–601PubMedGoogle Scholar
  29. 29.
    Katsanos KH, Elisaf M, Bairaktari E, Tsianos EV (2001) Severe hypomagnesemia and hypoparathyroidism in Kearns-Sayre syndrome. Am J Nephrol 21:150–153CrossRefPubMedGoogle Scholar
  30. 30.
    Tritschler HJ, Andreetta F, Moraes CT, Bonilla E, Arnaudo E, Danon MJ, Glass S, Zelaya BM, Vamos E, Teleman-Toppet (1992) Mitochondrial myopathy of childhood associated with depletion of mitochondrial DNA. Neurology 42:209–217PubMedGoogle Scholar
  31. 31.
    DiMauro S, Servidei S, Zeviani M, DiRocco M, DeVivo DC, DiDonato S, Uziel G, Berry K, Hoganson G, Johnsen SD (1987) Cytochrome C oxidase deficiency in Leigh syndrome. Ann Neurol 22:498–506Google Scholar
  32. 32.
    Campos Y, García-Silva MT, Barrionuevo CR, Cabello A, Muley R, Arenas J (1995) Mitochondrial DNA deletion in a patient with mitochondrial myopathy, lactic acidosis and stroke-like episodes (MELAS) and Fanconi’ syndrome. Pediatr Neurol 13:69–72CrossRefPubMedGoogle Scholar
  33. 33.
    Santos F, García Nieto V (2000) Exploración basal de la función renal. In: García Nieto V, Santos F (eds) Nefrología Pediátrica. Aula Médica S.A, Madrid, pp 3–14Google Scholar
  34. 34.
    De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, García Silva MT, Hernández EM, Lissens W, Van Coster R (2003) Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene. Am J Med Genet 121A:126–131CrossRefGoogle Scholar
  35. 35.
    Mori K, Narahara K, Ninomiya S, Goto Y, Nonaka I (1991) Renal and skin involvement in a patient with complete Kearns-Sayre syndrome. Am J Med Genet 38:583–587PubMedGoogle Scholar
  36. 36.
    Zupank ML, Moraes CT, Shanske S, Langman CB, Ciafalon E, DiMauro S (1991) Deletion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. Ann Neurol 29:680–683Google Scholar
  37. 37.
    Gurgey A, Ozalp I, Rötig A, Coskun T, Tekinalp G, Erdem G, Akeoren Z, Caglar M, Bakkaloglu A (1996) A case of Pearson syndrome associated with multiple renal cysts. Pediatr Nephrol 10:637–638CrossRefPubMedGoogle Scholar
  38. 38.
    Gilbert RD, Emms M (1996) Pearson’s syndrome presenting with Fanconi syndrome. Ultrastruct Pathol 20:473–475PubMedGoogle Scholar
  39. 39.
    Lonlay P, Valnot I, Barrientos A, Gorbatyuk M, Tzagoloff A, Taanman JW, Benayoun E, Chretien D, Kadhom N, Lombes A, de Baulny HO, Niaudet P, Munnich A, Rustin P, Rötig A (2001) A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure. Nat Genet 29:57–60CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2005

Authors and Affiliations

  • Elena Martín-Hernández
    • 1
  • M. Teresa García-Silva
    • 1
  • Julia Vara
    • 2
  • Yolanda Campos
    • 3
  • Ana Cabello
    • 4
  • Rafael Muley
    • 2
  • Pilar del Hoyo
    • 3
  • Miguel Angel Martín
    • 3
  • Joaquín Arenas
    • 3
  1. 1.Unidad de E. Mitocondriales—E. Metabólicas HereditariasDept. Pediatría, Hospital Doce de OctubreMadridSpain
  2. 2.NefrologíaDept. Pediatría, Hospital 12 de OctubreMadridSpain
  3. 3.Dept. de BioquímicaHospital 12 de OctubreMadridSpain
  4. 4.NeuropatologíaDept. de Anatomía Patológica, Hospital 12 de OctubreMadridSpain

Personalised recommendations