Fatal infantile mitochondrial cardiomyopathy and myopathy with heterogeneous tissue expression of combined respiratory chain deficiencies.
A 5-month-old boy died of progressive heart failure that started at the age of 3 months. Autopsy revealed a mitochondrial cardiomyopathy and a mitochondrial myopathy of the limb muscle and diaphragm. Cytochemically random defects of cytochrome c oxidase were visualized by light and electron microscopy in the diaphragm and especially the heart muscle, the limb muscle showing a diffuse attenuation whereas the liver and kidneys reacted normally. The activities of NADH-dehydrogenase (complex I) and cytochrome c oxidase (complex IV) were severely diminished (20% residual activity of controls) in the skeletal and heart muscle. In the heart, succinate cytochrome c reductase (complex II/III) was additionally decreased to the same degree. Loss of cytochrome c oxidase activity was based on a reduction of both mitochondrial and nuclear derived subunits in the heart and diaphragm as revealed by immunohistochemical analysis, whereas the limb muscle showed a normal immunoreactive protein content. The results illustrate heterogeneous tissue expression of respiratory chain enzyme defects and demonstrate that a cardiomyopathy may be the leading presentation of a mitochondrial disorder in early infancy.
Müller-Höcker
J
J
Pathologisches Institut, Universität München, Federal Republic of Germany.
Ibel
H
H
Paetzke
I
I
Deufel
T
T
Endres
W
W
Kadenbach
B
B
Gokel
J M
JM
Hübner
G
G
D009202:Cardiomyopathies / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000473:pathology*; D009135:Muscular Diseases / Q000150:complications / Q000201:enzymology / Q000473:pathology*; D009245:NADH Dehydrogenase / Q000172:deficiency
D009245:NADH Dehydrogenase