Scientific letters.

Heart transplantation in children with mitochondrial cardiomyopathy 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, cardiomy-opathy 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 car-diomyopathy. 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 cardiomy-opathy or unexplained sudden death. All patients were screened for skeletal myopathy, ocular myopathy, pigmentary retinopathy, and renal and liver dysfunction. Respiratory enzyme activities (cytochrome-c oxidase, suc-cinate cytochrome c reductase, and rotenone sensitive reduced nicotinamide adenine dinu-cleotide cytochrome c reductase) were spec-trophotometrically measured in homogenates from frozen endomyocardial biopsy specimens according to previously published procedures. 4 Skeletal muscle biopsy was performed in 6/7 patients. In addition, enzyme studies were performed in fibroblasts in 2/7 patients. Finally, one patient had a mild pro-teinuria and raised liver enzymes. She underwent a liver and kidney biopsy before heart transplantation. A complex I (NADH-ubiquinone reduct-ase) defect was diagnosed in two patients. This defect was confined to the myocardium in one patient, while another patient, with no evidence of clinical myopathy, expressed the defect in skeletal muscle as well. One patient had a complex III deficiency (ubiquinol cyto-chrome c reductase) in the myocardium but also in the kidney and liver. Four patients had a multiple defect limited to the myocardium : complex I + IV (cytochrome oxidase) in two patients, generalised defect in two twin sisters (table 1). Mitochondrial DNA deletions or point mutations previously reported in car-diomyopathy were not observed in these patients. Patient 7 had a mutation in the cd2 helix of the mitochondrial cytochrome b gene. One patient died while on the waiting list (patient 6). Orthotopic heart transplantation was performed in six children at our institution. Immunosuppressive prophylaxis included cyclosporine, azathioprine, and pred-nisone. Patient 7 died one month after heart transplantation because of dysfunction …