Genetic defects of mitochondrial energy supply can give rise to a variety of symptoms and virtually any organ or tissue can be involved.1 In particular, cardiomyopathy can be the presenting symptom of a respiratory enzyme deficiency in infancy. Alternatively, cardiomyopathy frequently occurs in the course of these diseases.2 Multi-organ involvement is usually regarded as a contraindication for heart transplantation in metabolic disorders. Yet, since the clinical expression of respiratory enzyme deficiency can be limited to the myocardium, it is reasonable to consider heart transplantation in mitochondrial cardiomyopathy.3 Here, we report on successful orthotopic heart transplantation in seven children (four girls, three boys) with severe mitochondrial cardiomyopathy. Mean (SD) age at time of diagnosis was 7.5 (6.1) years (range 1 month to 16 years). All had dilated cardiomyopathy with hypertrophied walls. Six had a positive family history of cardiomyopathy or unexplained sudden death. All patients were screened for skeletal myopathy, ocular myopathy, pigmentary retinopathy, and renal and liver dysfunction. Respiratory enzyme activities (cytochrome-coxidase, succinate cytochrome creductase, and rotenone sensitive reduced nicotinamide adenine dinucleotide cytochrome c reductase) were spectrophotometrically measured in homogenates from frozen endomyocardial biopsy specimens according to previously published procedures.4 Skeletal …