Exercise intolerance due to cytochrome b mutation.

Area of Science:

• Mitochondrial Medicine
• Genetics
• Exercise Physiology

Background:

• Exercise intolerance is a debilitating condition with diverse etiologies.
• Mitochondrial disorders, particularly those affecting the respiratory chain, are recognized causes of exercise intolerance.
• Mutations in mitochondrial DNA, specifically in genes encoding respiratory chain components, can lead to impaired cellular energy production.

Observation:

• A case of an 18-year-old male presenting with lifelong exercise intolerance, resting lactic acidosis, and ragged-red fibers on muscle biopsy is described.
• The patient exhibited isolated muscle complex III deficiency, a rare form of mitochondrial dysfunction.
• Genetic analysis revealed a heteroplasmic m.14849T>C mutation in the cytochrome b gene.

Findings:

• The identified m.14849T>C mutation in the cytochrome b gene is a novel cause of mitochondrial disease.
• This mutation leads to a specific deficiency in muscle complex III activity, impacting the electron transport chain.
• Review of previously reported cases with cytochrome b mutations reinforces the link between these genetic defects and exercise intolerance.

Implications:

• The presence of COX-positive ragged-red fibers, exercise intolerance, and lactic acidemia serves as a diagnostic clue for this specific mitochondrial disorder.
• Understanding the genetic basis of mitochondrial complex III deficiency expands diagnostic capabilities for patients with unexplained exercise intolerance.
• This research highlights the importance of genetic testing in the diagnosis of rare mitochondrial myopathies and exercise intolerance.