Learning Objective: By the end of this lesson, the learner will be able to describe the inheritance, pathophysiology, clinical features, and key examples of mitochondrial diseases, including mitochondrial myopathies and Leber hereditary optic neuropathy.
Key Concepts
- Inheritance: Mitochondrial (maternal) → all offspring of affected mothers may be affected; males do not transmit
- Pathophysiology: Defects in oxidative phosphorylation → ↓ ATP production
- High-energy tissues most affected: CNS, skeletal muscle, heart, retina
Mitochondrial Myopathies
- MELAS – Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes
- Features: stroke-like episodes before age 40, lactic acidosis, seizures, myopathy
- MERRF – Myoclonic Epilepsy with Ragged Red Fibers
- Features: myoclonus, seizures, ataxia, ragged red fibers on muscle biopsy
Muscle Biopsy Findings:
- Light microscopy: ragged red fibers (accumulation of abnormal mitochondria)
- Electron microscopy: mitochondrial crystalline inclusions
Leber Hereditary Optic Neuropathy (LHON)
- Mutation: Complex I of the electron transport chain
- Inheritance: maternal
- Features: subacute bilateral vision loss in teens/young adults (males > females), often permanent
- May be associated with neurologic dysfunction (tremors, MS-like symptoms)
High-Yield Tips
- Maternal inheritance: only mothers transmit mtDNA
- Ragged red fibers = classic mitochondrial myopathy
- Tissues affected: high-energy → CNS, skeletal muscle, retina
- Examples: MELAS, MERRF, LHON
