Definition: A group of disorders characterized by an impaired energy production that mainly affects organs with a high energy requirement (e.g., brain).

Epidemiology

Etiology

Caused by defects in mitochondrial DNA, which are maternally inherited

• Children of an affected mother will likewise be affected.
• Genetic expression is variable due to heteroplasmy.

Pathophysiology

• Impaired oxidative phosphorylation → decreased production of energy in mitochondria (lack of ATP) → up-regulation of glycolysis → overproduction of pyruvate → accumulation of lactate and alanine
• Organs with a high energy requirement (e.g., retina, brain, inner ear, skeletal, cardiac muscles) are particularly affected.

Clinical features

• Commonly external ophthalmoplegia, ptosis, and/or exertional muscle weakness.

Subtypes of mitochondrial myopathies

• MELAS: characterized by Mitochondrial Encephalomyopathy, Lactic Acidosis, recurring Stroke-like episodes
  • Other findings include
    • Muscle weakness
    • Tonic-clonic seizures

Diagnostics

• Genetic studies (including mitochondrial DNA)
• Muscle biopsy: Immunohistochemistry typically shows ragged red fibers, which are caused by subsarcolemmal and intermyofibrillar accumulation of defective mitochondria in muscles (mitochondria stain red).
• Laboratory studies
  • Normal CK
    • Mitochondrial myopathies often cause mitochondrial dysfunction, which can lead to muscle weakness without significant muscle fiber death.
  • Elevated lactate and alanine in serum, urine and/or CSF → lactic acidosis

Treatment