[Clinical, biochemical and genetic analysis of the mitochondrial disorders presenting with cardiac damage].
OBJECTIVE
Mitochondrial disease is a group of energy metabolic disorders, characterized by involvement of multisystem with high energy requirements. Encephalomyopathies are common clinical findings of the mitochondrial diseases. However, mitochondrial cardiac damage is not rare. In this study, the clinical, biological, and genetic analyses were performed in three patients with mitochondrial cardiac damage, in order to understand the characteristics of mitochondrial diseases.


METHODS
Three girls presented with arrhythmia and cardiac enlargement from the age of 3, 4 and 8 years respectively. They were admitted into the Peking University First Hospital. Infection, autoimmune diseases, aminoacidopathies, organic acidurias, mitochondrial-fatty acid oxidation defects, and lysosomal storage disease were excluded by routine laboratory examinations and metabolic analysis for blood amino acids, acylcarnitines, urinary organic acids, and lysosome activity assay. Peripheral leukocytes mitochondrial respiratory chain enzyme I to V activities were measured by spectrophotometry. The entire sequence of the mitochondrial DNA was analyzed.


RESULTS
In two patients (case 1 and case 3), hypertrophic cardiomyopathy and grade I to grade II of cardiac function were found. One patient (case 2) was diagnosed with arrhythmia and grade I of cardiac function. Increased creatine phosphokinase and creatine kinase isoenzyme MB were observed. Mitochondrial respiratory chain complex deficiencies were indentified in the three patients. Patient 1 had combined deficiencies of complex III and V. The activity of complex I+III was 18.7 nmol/(min·mg mitochondrial protein) (control 84.4 ± 28.5). The activity of complex V was 20.4 nmol/(min·mg mitochondrial protein) (control 103.7 ± 29.2). In her mitochondrial gene, A14693G on tRNA(Glu) and T16519C on D-loop were found. Patient 2 had an isolated complex I deficiency. The activity was 22.0 nmol/(min·mg mitochondrial protein) (control 44.0 ± 5.4). A16183C, T16189C and G15043A mutations on D-loop were found. Patient 3 had a combined deficiency of complex IV and V. The activity of complex IV was 21.0 nmol/(min·mg mitochondrial protein) (control 54.1 ± 12.3). The activity of complex V was 23.2 nmol/(min·mg mitochondrial protein) (control 103.7 ± 29.2). C253T and C16187T mutations on D-loop were detected. Haplotype analysis showed that three patients belong to H2a2a. Improvement was observed after the treatment with L-carnitine, coenzyme Q10, vitamin C and E. At present, the patients are 7, 5 and 8 years old. Although excise intolerance still persists, they had a good general condition with normal school life.


CONCLUSIONS
The mitochondrial diseases with cardiac damage show cardiomyopathy, arrhythmia and exercise intolerance. Many kinds of mitochondrial respiratory chain deficiency were observed. A14693G in mitochondrial tRNA(Glu) gene is probably one of the causes in China.
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Yan-yan
YY
Ma
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Tong-fei
TF
Wu
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Yu-peng
YP
Liu
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Qiao
Q
Wang
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Xi-yuan
XY
Li
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Yuan
Y
Ding
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
Jin-qing
JQ
Song
Department of Pediatrics, Peking University First Hospital, Beijing 100034, China. Email: organic.acid@126.com.
Yan-ling
YL
Yang
D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009154:Mutation
D015415:Biomarkers; D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins