Progressive myopathy with a combined respiratory chain defect including Complex II

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mitochondrial respiratory chain defects typically involve Complexes I, III, and IV, often due to DNA mutations.
• Combined defects, especially those including Complex II, are rare and primarily manifest as muscular symptoms like weakness and exercise intolerance.

Observation:

• A patient presented with fatal progressive myopathy, characterized by reduced succinate dehydrogenase activity, ragged red fibers, and lipid accumulation in muscle biopsies.
• Histochemistry revealed varying Cytochrome c oxidase (COX) activity, with 30% of fibers showing increased subsarcolemmal staining and 27% being COX negative.

Findings:

• Western blotting confirmed reduced expression of subunits for Complex I, Complex II, and Complex IV.
• The patient exhibited a complex mitochondrial dysfunction impacting multiple respiratory chain complexes and fatty acid metabolism.

Implications:

• This case introduces a novel histological pattern associated with combined respiratory chain deficiencies involving Complex II.
• The findings suggest that such complex mitochondrial disorders can be fatal and progress rapidly, emphasizing the need for early diagnosis.