Heart Transplantation for Progressive Cardiomyopathy as a Manifestation of MELAS Syndrome

Department of Surgery, University of North Carolina at Chapel Hill, North Carolina, United States
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 6.65). 01/2006; 24(12):2286-9. DOI: 10.1016/j.healun.2005.05.012
Source: PubMed


Mitochondrial diseases represent a heterogeneous group of disorders associated with a wide array of clinical manifestations. The presentation of patients with mitochondrial pathology largely depends upon the dysfunction of organ systems with large metabolic/energy requirements, including cardiac, neurologic, and musculoskeletal. In particular, mitochondrial myocardial disease can be progressive resulting in congestive heart failure and end-stage heart disease. This article reviews the role of heart transplantation for a particular variant of mitochondrial disorder, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, and discusses perioperative management issues related to transplantation for mitochondrial cardiomyopathies.

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    • "Pacemakers are recommended for all patients with neuromuscular diseases (including KSS) who have developed atrioventricular (AV) block, however, prophylactic pacemaker placement prior to the development of third-degree or advanced second-degree AV block is discussed with patients and families as well [16]. Based on the International Society of Heart and Lung Transplantation database, 6 patients who received heart transplantation between 1990 and 2003 had a diagnosis of myopathy due to a mitochondrial pathology [17]. "
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    ABSTRACT: Background Kearns-Sayre Syndrome (KSS) is a multisystem disorder caused by a dysfunction of the oxidative phosphorylation system within mitochondria. Mitochondrial DNA (mtDNA) rearrangements are a key molecular feature of this disease, which manifest a broad phenotypic spectrum. Case presentation Here, we present a boy with KSS whose symptoms included cardiac conduction deficit, cardiomyopathy and growth hormone (GH) deficiency. The patient showed typical symptoms for KSS from early childhood (chronic progressive external ophthalmoplegia, retinopathy, short stature). Long-range PCR analysis disclosed a 7663-base pair heteroplasmic deletion in the mtDNA encompassing nucleotides 6340–14003. At 12 years of age, GH deficiency was recognized and recombinant growth hormone (rGH) therapy was started. At 15 years of age, a complete atrioventicular block was diagnosed and the patient received a pacemaker. During the following 6 months, progressive deterioration of the left ventricle was observed and an echocardiogram showed features of dilated cardiomyopathy. The rGH treatment was then discontinued at a final height of 163 cm. Unfortunately, due to multi-organ insufficiency and inflammation, the patient died at the age of 18 years. Conclusions The response to rGH therapy in the patient was very satisfactory. The large mtDNA deletion had no apparent impact on the response to rGH. Cardiac disturbances occurred as part of the syndrome and were not related to rGH therapy; however, the progression of the disease led to death.
    BMC Pediatrics 02/2013; 13(1):27. DOI:10.1186/1471-2431-13-27 · 1.93 Impact Factor
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    • "rate has been reported in six patients with mitochondrial cardiomyopathy (Bonnet et al. 2001). More recently, a successful recipient outcome for two patients with MELAS was reported (Bhati et al. 2005). Liver function is often impaired, especially in mtDNA depletion syndromes. "
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    ABSTRACT: Mitochondrial disorders can no longer be ignored in most medical disciplines. Such disorders include specific and widespread organ involvement, with tissue degeneration or tumor formation. Primary or secondary actors, mitochondrial dysfunctions also play a role in the aging process. Despite progresses made in identification of their molecular bases, nearly everything remains to be done as regards therapy. Research dealing with mitochondrial physiology and pathology has >20 years of history around the world. We are involved, as are many other laboratories, in the challenge of finding ways to fight these diseases. However, our main limitation is the scarcety of animal models required for both understanding the molecular mechanisms underlying the diseases and evaluating therapeutic strategies. This is especially true for diseases due to mutations in mitochondrial DNA (mtDNA), since an authentic genetic model of mtDNA mutations is technically a very difficult task due to both the inability of manipulating the mitochondrial genome of living mammalian cells and to its multicopy nature. This has led researchers in the field to consider the prospect of gene therapy approaches that can roughly be divided into three groups: (1) import of wild-type copies or relevant sections of DNA or RNA into mitochondria, (2) manipulation of mitochondrial genetic content, and (3) rescue of a defect by expression of an engineered gene product from the nucleus (allotopic or xenotropic expression). We briefly introduce these concepts and indicate where promising progress has been made in the last decade.
    Journal of Inherited Metabolic Disease 04/2011; 34(2):327-44. DOI:10.1007/s10545-010-9131-5 · 3.37 Impact Factor
  • T Ozawa ·
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    ABSTRACT: Accumulating evidence emphasizes the role of genetic factors in the development of cardiomyopathy. Mitochondrial cardiomyopathy is defined as cardiomyopathy caused by mitochondrial DNA mutations. The rate of mitochondrial DNA mutation is estimated to be much higher than that of nuclear DNA. It has been demonstrated that mutations of mitochondrial DNA are found in a variety of diseases, suggesting a new concept of mitochondrial disease. This contribution reviews the concept, molecular genetics, family history, pathology, clinical symptoms, diagnosis and therapy of mitochondrial cardiomyopathy.
    Herz 05/1994; 19(2):105-18, 125. DOI:10.1007/978-1-84996-471-5_7 · 0.69 Impact Factor
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