Pediatrics & Neonatology
Volume 49, Issue 4 , Pages 145-149, August 2008

Mutation of Mitochondrial DNA G13513A Presenting with Leigh Syndrome, Wolff-Parkinson-White Syndrome and Cardiomyopathy

  • Shi-Bing Wang

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Wen-Chin Weng

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Ni-Chung Lee

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Wuh-Liang Hwu

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Pi-Chuan Fan

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Wang-Tso Lee

      Affiliations

    • Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
    • Corresponding Author InformationCorresponding author. Department of Pediatrics, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei 100, Taiwan

Received 3 March 2008; received in revised form 18 April 2008; accepted 28 August 2008.

Article Outline

Mutation of mitochondrial DNA (mtDNA) G13513A, encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and Leigh syndrome. Wolff-Parkinson-White (WPW) syndrome and optic atrophy were reported in a high proportion of patients with this mutation. We report an 18-month-old girl, with an 11-month history of psychomotor regression who was diagnosed with WPW syndrome and hypertrophic cardiomyopathy, in association with Leigh syndrome. Supplementation with coenzyme Q10, thiamine and carnitine prevented further regression in gross motor function but the patient's heart function deteriorated and dilated cardiomyopathy developed 11 months later. She was found to have a mutation of mtDNA G13513A. We suggest that mtDNA G13513A mutation is an important factor in patients with Leigh syndrome associated with WPW syndrome and/or optic atrophy, and serial heart function monitoring by echocardiography is recommended in this group of patients.

KEY WORDS:  cardiomyopathy , electron transfer complex I , Leigh syndrome , Wolff-Parkinson-White syndrome

No full text is available. To read the body of this article, please view the PDF online.

 

Back to Article Outline

References 

  1. Schmiedel J , Jackson S , Schafer J , Reichmann H . Mitochondrial cytopathies . J Neurol . 2003;250:267–277
  2. Chol M , Lebon S , Benit P , et al.   The mitochondrial DNA G13513A MELAS mutation in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency . J Med Genet . 2003;40:188–191
  3. Santorelli FM , Tanji K , Kulikova R , et al.   Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS . Biochem Biophys Res Commun . 1997;238:326–328
  4. Bugiani M , Invernizzi F , Alberio S , et al.   Clinical and molecular findings in children with complex I deficiency . Biochim Biophys Acta . 2004;1659:136–147
  5. Kirby DM , Boneh A , Chow CW , et al.   Low mutant load of mitochondrial DNA G13513A mutation can cause Leigh's disease . Ann Neurol . 2003;54:473–478
  6. Ruiter EM , Siers MH , van den Elzen C , et al.   The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White . Eur J Hum Genet . 2007;15:155–161
  7. Sudo A , Honzawa S , Nonaka I , Goto Y . Leigh syndrome caused by mitochondrial DNA G13513A mutation: frequency and clinical features in Japan . J Hum Genet . 2004;49:92–96
  8. Blok MJ , Spruijt L , de Coo IF , Schoonderwoerd K , Hendrickx A , Smeets HJ . Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease. J Med Genet 2007;44:e74. 9. Cardol P, Boutaffala L, Memmi S, Devreese B, Matagne RF, Remacle C. In Chlamydomonas, the loss of ND5 subunit prevents the assembly of whole mitochondrial complex I and leads to the formation of a low abundant 700 kDa subcomplex . Biochim Biophys Acta . 2008;1777:388–396
  9. Marin-Garcia J , Goldenthal MJ . Understanding the impact of mitochondrial defects in cardiovascular disease: a review . J Card Fail . 2002;8:347–361
  10. Mashima Y , Kigasawa K , Hasegawa H , Tani M , Oguchi Y . High incidence of pre-excitation syndrome in Japanese families with Leber's hereditary optic neuropathy . Clin Genet . 1996;50:535–537
  11. Nikoskelainen EK , Savontaus ML , Huoponen K , Antila K , Hartiala J . Pre-excitation syndrome in Leber's hereditary optic neuropathy . Lancet . 1994;344:857–858
  12. Sproule DM , Kaufmann P , Engelstad K , Starc TJ , Hordof AJ , De Vivo DC . Wolff-Parkinson-White syndrome in patients with MELAS . Arch Neurol . 2007;64:1625–1627
  13. Peters NS , Rowland E , Bennett JG , Green CR , Anderson RH , Severs NJ . The Wolff-Parkinson-White syndrome: the cellular substrate for conduction in the accessory atrioventricular pathway . Eur Heart J . 1994;15:981–987
  14. Gollob MH , Green MS , Tang AS , et al.   Identification of a gene responsible for familial Wolff-Parkinson-White syndrome . N Engl J Med . 2001;344:1823–1831
  15. Hardie DG , Carling D . The AMP-activated protein kinasefuel gauge of the mammalian cell? . Eur J Biochem . 1997;246:259–273
  16. Yaplito-Lee J , Weintraub R , Jamsen K , Chow CW , Thorburn DR , Boneh A . Cardiac manifestations in oxidative phosphorylation disorders of childhood . J Pediatr . 2007;150:407–411
  17. Silvestri G , Santorelli FM , Shanske S , et al.   A new mtDNA mutation in the tRNA(Leu(UUR)) gene associated with maternally inherited cardiomyopathy . Hum Mutat . 1994;3:37–43
  18. Scaglia F , Towbin JA , Craigen WJ , et al.   Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease . Pediatrics . 2004;114:925–931
  19. Hayashi N , Geraghty MT , Green WR . Ocular histopathologic study of a patient with the T 8993-G point mutation in Leigh's syndrome . Ophthalmology . 2000;107:1397–1402
  20. Carelli V , La Morgia C , Iommarini L , et al.   Mitochondrial optic neuropathies: how two genomes may kill the same cell type? . Biosci Rep . 2007;27:173–184

PII: S1875-9572(08)60030-3

doi:10.1016/S1875-9572(08)60030-3

Pediatrics & Neonatology
Volume 49, Issue 4 , Pages 145-149, August 2008

Article Tools