Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: An unrecognized clinical entity in young, asymptomatic adults

European Heart Journal

Volumn 37, Issue 32, 2016, Pages 2552-2559

  Ng, Yi Shiau ^a   Grady, John P ^a   Lax, Nichola Z ^a   Bourke, John P ^b   Alston, Charlotte L ^a   Hardy, Steven A ^a   Falkous, Gavin ^a   Schaefer, Andrew G ^a   Radunovic, Aleksandar ^c   Mohiddin, Saidi A ^d   Ralph, Matilda ^e   Alhakim, Ali ^f   Taylor, Robert W ^a   McFarland, Robert ^a   Turnbull, Douglass M ^a   Gorman, Gráinne S ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b FREEMAN HOSPITAL   (United Kingdom)

^c ROYAL LONDON HOSPITAL   (United Kingdom)

^d LONDON CHEST HOSPITAL   (United Kingdom)

^e Hemel Hempstead General Hospital   (United Kingdom)

^f EAST SURREY HOSPITAL   (United Kingdom)

Author keywords

Cardiac; Genetic autopsy; m.3243A>G; Sudden death

Indexed keywords

CYTOCHROME C OXIDASE; MITOCHONDRIAL DNA; PROBIOTIC AGENT; SUCCINATE DEHYDROGENASE; SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIDECARENONE; VITAMIN B COMPLEX;

ADULT; ADULT DISEASE; AGED; ALCOHOL BLOOD LEVEL; ALCOHOL CONSUMPTION; ARTICLE; AUTOPSY; CARDIAC MUSCLE; CARDIOMYOPATHY; CAUSE OF DEATH; CEREBELLUM ATROPHY; CLINICAL ARTICLE; DIETARY SUPPLEMENT; DISORDERS OF MITOCHONDRIAL FUNCTIONS; EXTENDED FAMILY; FAMILY HISTORY; FEMALE; GENETIC SCREENING; HEARING IMPAIRMENT; HEART ARRHYTHMIA; HEART ATRIUM; HEART LEFT VENTRICLE HYPERTROPHY; HEART VENTRICLE; HETEROPLASMY; HUMAN; HUMAN TISSUE; IRRITABLE COLON; MALE; MEDIAN SURVIVAL TIME; MELAS SYNDROME; MIDDLE AGED; MUTATIONAL LOAD; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; POINT MUTATION; PRIORITY JOURNAL; RESPIRATORY CHAIN; SUDDEN ADULT DEATH SYNDROME; SUDDEN DEATH; MITOCHONDRION; MUTATION;

ADULT; DEATH, SUDDEN; DNA, MITOCHONDRIAL; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DISEASES; MUTATION;

EID: 84994795013     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehv306     Document Type: Article

References (39)

1. Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet 2008;83:254-260.
2. Manwaring N, Jones MM, Wang JJ, Rochtchina E, Howard C, Mitchell P, Sue CM. Population prevalence of the MELAS A3243G mutation. Mitochondrion 2007;7: 230-233.
3. Majamaa K, Moilanen JS, Uimonen S, Remes AM, Salmela PI, Karppa M, Majamaa-Voltti KA, Rusanen H, Sorri M, Peuhkurinen KJ, Hassinen IE. Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population. American Journal of Human Genetics 1998;63:447-454.
4. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol 2015;77:753-759.
5. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP. Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 1984;16:481-488.
6. Moraes CT, Ciacci F, Silvestri G, Shanske S, Sciacco M, Hirano M, Schon EA, Bonilla E, DiMauro S. Atypical clinical presentations associated with the MELAS mutation at position 3243 of human mitochondrial DNA. Neuromuscul Disord 1993; 3:43-50.
7. Murphy R, Turnbull DM,Walker M, Hattersley AT. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A.G mitochondrial point mutation. Diabet Med 2008;25:383-399.
8. Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R. The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A.G mutation - implications for diagnosis and management. J Neurol Neurosurg Psychiatry 2013;84: 936-938.
9. Bates MGD, Newman JH, Jakovljevic DG, Hollingsworth KG, Alston CL, Zalewski P, Klawe JJ, Blamire AM, MacGowan GA, Keavney BD, Bourke JP, Schaefer A, McFarland R, Newton JL, Turnbull DM, Taylor RW, Trenell MI, Gorman GS. Defining cardiac adaptations and safety of endurance training in patients with m.3243A.G-related mitochondrial disease. Int J Cardiol 2013;168: 3599-3608.
10. Holmgren D,Wåhlander H, Eriksson BO, Oldfors A, Holme E, Tulinius M. Cardiomyopathy in children with mitochondrial disease: clinical course and cardiological findings. Eur Heart J 2003;24:280-288.
11. Majamaa-Voltti K, Turkka J, Kortelainen ML, Huikuri H, Majamaa K. Causes of death in pedigrees with the 3243A.G mutation in mitochondrial DNA. J Neurol Neurosurg Psychiatry 2008;79:209-211.
12. Malfatti E, Laforet P, Jardel C, Stojkovic T, Behin A, Eymard B, Lombes A, Benmalek A, Becane HM, Berber N, Meune C, Duboc D,Wahbi K. High risk of severe cardiac adverse events in patients with mitochondrial m.3243A.G mutation. Neurology 2013;80:100-105.
13. Klopstock TM, Jaksch MM, Gasser TM. Age and cause of death in mitochondrial diseases. Neurology 1999;53:855-857.
14. Kaufmann P, Engelstad K, Wei Y, Kulikova R, Oskoui M, Sproule DM, Battista V, Koenigsberger DY, Pascual JM, Shanske S, Sano M, Mao X, Hirano M, Shungu DC, Dimauro S, De Vivo DC. Natural history of MELAS associated with mitochondrial DNA m.3243A.G genotype. Neurology 2011;77:1965-1971.
15. Old SL, Johnson MA. Methods of microphotometric assay of succinate dehydrogenase and cytochrome c oxidase activities for use on human skeletal muscle. Histochem J 1989;21:545-555.
16. Betts J, Jaros E, Perry RH, Schaefer AM, Taylor RW, Abdel-All Z, Lightowlers RN, Turnbull DM. Molecular neuropathology of MELAS: level of heteroplasmy in individual neurones and evidence of extensive vascular involvement. Neuropathol Appl Neurobiol 2006;32:359-373.
17. Lax NZ, Whittaker RG, Hepplewhite PD, Reeve AK, Blakely EL, Jaros E, Ince PG, Taylor RW, Fawcett PR, Turnbull DM. Sensory neuronopathy in patients harbouring recessive polymerase gamma mutations. Brain 2012;135(Pt 1):62-71.
18. de la Grandmaison GL, Clairand I, Durigon M. Organ weight in 684 adult autopsies: new tables for a Caucasoid population. Forensic Sci Int 2001;119:149-154.
19. Dekaban AS, Sadowsky D. Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights. Ann Neurol 1978;4: 345-356.
20. Alston CL, He L, Morris AA, Hughes I, de Goede C, Turnbull DM, McFarland R, Taylor RW. Maternally inherited mitochondrial DNA disease in consanguineous families. Eur J Hum Genet 2011;19:1226-1229.
21. Cox DR. Regression Models and Life-Tables. J R Stat Soc Ser B (Methodological) 1972; 34:187-220.
22. Bates MG, Bourke JP, Giordano C, d'Amati G, Turnbull DM, Taylor RW. Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management. Eur Heart J 2012;33:3023-3033.
23. Okajima Y, Tanabe Y, Takayanagi M, Aotsuka H. A follow up study of myocardial involvement in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Heart 1998;80:292-295.
24. Majamaa-Voltti K, Peuhkurinen K, Kortelainen M-L, Hassinen I, Majamaa K. Cardiac abnormalities in patients with mitochondrial DNA mutation 3243A.G. BMC Cardiovasc Disord 2002;2:12.
25. Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum. Comparison of fetuses and infants with and without congenital heart disease and patients with hypertrophic cardiomyopathy. Circulation 1979;60:685-696.
26. Shirani J, Pick R, Roberts WC, Maron BJ. Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death. J Am Coll Cardiol 2000;35:36-44.
27. Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med 2000;342:1778-1785.
28. Morgan-Hughes JA, Darveniza P, Landon DN, Land JM, Clark JB. A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity. J Neurol Sci 1979;43:27-46.
29. Siler SQ, Neese RA, Christiansen MP, Hellerstein MK. The inhibition of gluconeogenesis following alcohol in humans. Am J Physiol 1998;275(5 Pt 1):E897-E907.
30. Shorvon S, Tomson T. Sudden unexpected death in epilepsy. Lancet 2011;378: 2028-2038.
31. Morentin B, Paz Suarez-Mier M, Audicana C, Aguilera B, Manuel Garamendi P, Elexpe X. Incidence and causes of sudden death in persons less than 36 years of age. Med Clin (Barc) 2001;116:281-285.
32. Papadakis M, Sharma S, Cox S, Sheppard MN, Panoulas VF, Behr ER. The magnitude of sudden cardiac death in the young: a death certificate-based review in England and Wales. Europace 2009;11:1353-1358.
33. Winkel BG, Holst AG, Theilade J, Kristensen IB, Thomsen JL, Ottesen GL, Bundgaard H, Svendsen JH, Haunsø S, Tfelt-Hansen J. Nationwide study of sudden cardiac death in persons aged 1-35 years. Eur Heart J 2011;32:983-990.
34. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol 2003;42: 1959-1963.
35. Wisten A, Forsberg H, Krantz P, Messner T. Sudden cardiac death in 15-35-year olds in Sweden during 1992-99. J Intern Med 2002;252:529-536.
36. O'Mahony C, Jichi F, Pavlou M, Monserrat L, Anastasakis A, Rapezzi C, Biagini E, Gimeno JR, Limongelli G, McKennaWJ, Omar RZ, Elliott PM. A novel clinical risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM risk-SCD). Eur Heart J 2014;35:2010-2020.
37. Elliott PM, Anastasakis A, Borger MA, Borggrefe M, Cecchi F, Charron P, Hagege AA, Lafont A, Limongelli G, Mahrholdt H, McKenna WJ, Mogensen J, Nihoyannopoulos P, Nistri S, Pieper PG, Pieske B, Rapezzi C, Rutten FH, Tillmanns C, Watkins H. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014;35:2733-2779.
38. Hollingsworth KG, Gorman GS, Trenell MI, McFarland R, TaylorRW, Turnbull DM, MacGowan GA, Blamire AM, Chinnery PF. Cardiomyopathy is common in patients with the mitochondrial DNA m.3243A.G mutation and correlates with mutation load. Neuromuscul Disord 2012;22:592-596.
39. Schaefer AM, Bates MGD, Bourke JP, McFarland R, Turnbull DM. Newcastle mitochondrial disease guidelines-cardiac involvement in adult mitochondrial disease: screening and initial management (Updated in 2013). http://www.newcastlemitochondria. com/wp-content/uploads/2012/09/Cardiology-Guidelines.pdf (30th October 2014).