A 27-year-old man was admitted to hospital because of severe cardiac failure. Investigation revealed dilated cardiomyopathy with a left ventricular ejection fraction of 15–20%. During adolescence the patient had been investigated for growth retardation and he also had progressive external ophthalmoplegia. There had been no symptoms of cardiac disease until 2 weeks before admittance. An endomyocardial biopsy showed cardiomyocytes deficient in cytochrome c oxidase (COX) in a mosaic pattern. A skeletal muscle biopsy showed mitochondrial myopathy with COX-deficient ragged-red fibers. Molecular genetic analysis revealed a heteroplasmic, 3.8-kb, mitochondrial DNA (mtDNA) deletion in heart and muscle. PCR-based quantification of the proportion of mtDNA with deletion showed 47% mutated mtDNA in the myocardial biopsy and 68% in muscle. In spite of treatment, the condition deteriorated and the patient died 5 days after admittance. This case demonstrates that mtDNA deletions may occasionally be the cause of severe dilated cardiomyopathy, and that morphological and molecular genetic diagnosis may be obtained by endomyocardial biopsy.

1.
Holt IJ, Harding AE, Cooper JM, Schapira AH, Toscano A, Clark JB, Morgan-Hughes JA: Mitochondrial myopathies: Clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DNA. Ann Neurol 1989;26:699–708.
2.
Berenberg RA, Pellock JM, DiMauro S, Schotland DL, Bonilla E, Eastwood A, Hays A, Vicale CT, Behrens M, Chutorian A, Rowland LP: Lumping or splitting? ‘Ophthalmoplegia plus’ or Kearns-Sayre syndrome? Ann Neurol 1977;1:37–54.
3.
Moslemi AR, Melberg A, Holme E, Oldfors A: Clonal expansion of mitochondrial DNA with multiple deletions in autosomal dominant progressive external ophthalmoplegia. Ann Neurol 1996;40:707–713.
4.
Moslemi AR, Melberg A, Holme E, Oldfors A: Autosomal dominant progressive external ophthalmoplegia: Distribution of multiple mitochondrial DNA deletions. Neurology 1999;53:79–84.
5.
Guenthard J, Wyler F, Fowler B, Baumgartner R: Cardiomyopathy in respiratory chain disorders. Arch Dis Child 1995;72:223–226.
6.
Anan R, Nakagawa M, Miyata M, Higuchi I, Nakao S, Suehara M, Osame M, Tanaka H: Cardiac involvement in mitochondrial diseases: A study on 17 patients with documented mitochondrial DNA defects. Circulation 1995;91:955–961.
7.
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.
8.
Santorelli FM, Mak SC, Vazquezacevedo M, Gonzalezastiazaran A, Ridaurasanz C, Gonzalezhalphen D, DiMauro S: A novel mitochondrial DNA point mutation associated with mitochondrial encephalocardiomyopathy. Biochem Biophys Res Commun 1995;216:835–840.
9.
Zeviani M, Gellera C, Antozzi C, Rimoldi M, Morandi L, Villani F, Tiranti V, Didonato S: Maternally inherited myopathy and cardiomyopathy – Association with mutation in mitochondrial DNA transfer-RNA-Leu(UUR). Lancet 1991;338:143–147.
10.
Silvestri G, Santorelli FM, Shanske S, Whitley CB, Schimmenti LA, Smith SA, DiMauro S: A new mtDNA mutation in the tRNA [Leu(UUR)] gene associated with maternally inherited cardiomyopathy. Hum Mutat 1994;3:37–43.
11.
Merante F, Tein I, Benson L, Robinson BH: Maternally inherited hypertrophic cardiomyopathy due to a novel T-to-C transition at nucleotide 9997 in the mitochondrial tRNA (glycine) gene. Am J Hum Genet 1994;55:437–446.
12.
Santorelli FM, Mak SC, Elschahawi M, Casali C, Shanske S, Baram TZ, Madrid RE, DiMauro S: Maternally inherited cardiomyopathy and hearing loss associated with a novel mutation in the mitochondrial tRNA(Lys) gene (G8363A). Am J Hum Genet 1996;58:933–939.
13.
Suomalainen A, Paetau A, Leinonen H, Majander A, Peltonen L, Somer H: Inherited idiopathic dilated cardiomyopathy with multiple deletions of mitochondrial DNA. Lancet 1992;340:1319–1320.
14.
Bohlega S, Tanji K, Santorelli FM, Hirano M, Aljishi A, DiMauro S: Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy. Neurology 1996;46:1329–1334.
15.
Tranchant C, Mousson B, Mohr M, Dumoulin R, Welsch M, Weess C, Stepien G, Warter JM: Cardiac transplantation in an incomplete Kearns-Sayre syndrome with mitochondrial DNA deletion. Neuromuscul Disord 1993;3:561–566.
16.
Müller-Höcker J, Seibel P, Schneiderbanger K, Zietz C, Obermaierkusser B, Gerbitz KD, Kadenbach B: In situ hybridization of mitochondrial DNA in the heart of a patient with Kearns-Sayre syndrome and dilatative cardiomyopathy. Hum Pathol 1992;23:1431–1437.
17.
Oldfors A, Larsson NG, Holme E, Tulinius M, Kadenbach B, Droste M: Mitochondrial DNA deletions and cytochrome-c oxidase deficiency in muscle fibres. J Neurol Sci 1992;110:169–177.
18.
Wang J, Wilhelmsson H, Graff C, Li H, Oldfors A, Rustin P, Bruning JC, Kahn CR, Clayton DA, Barsh GS, Thoren P, Larsson NG: Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet 1999;21:133–137.
19.
Larsson NG, Holme E, Kristiansson B, Oldfors A, Tulinius M: Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res 1990;28:131–136.
20.
Müller-Höcker J, Jacob U, Seibel P: The common 4977 base pair deletion of mitochondrial DNA preferentially accumulates in the cardiac conduction system of patients with Kearns-Sayre syndrome. Modern Pathol 1998;11:295–301.
21.
Moslemi AR, Tulinius M, Holme E, Oldfors A: Threshold expression of the tRNA(Lys) A8344G mutation in single muscle fibres. Neuromuscul Disord 1998;8:345–349.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.