Whilst most DNA is found in the cell nucleus, a small amount of double-stranded DNA is present in the mitochondria. It encodes protein components of the respiratory chain and some special types of RNA

Mitochondrial inheritance has the following characteristics:

• inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
• none of the children of an affected male will inherit the disease
• all of the children of an affected female will inherit the disease
• generally, encode rare neurological diseases
• poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy

Common clinical features of mitochondrial disorders

• neurological
  • seizures
  • developmental delay / learning difficulties
  • ataxia, spasticity, peripheral neuropathy
  • stroke-like episodes (esp. MELAS)
  • sensorineural hearing loss
  • ophthalmoplegia and ptosis
• muscular
  • proximal myopathy, exercise intolerance
  • lactic acidosis (due to impaired oxidative phosphorylation)
• ocular
  • optic atrophy (e.g. Leber’s hereditary optic neuropathy, LHON)
  • pigmentary retinopathy
• cardiac
  • cardiomyopathy (hypertrophic or dilated)
  • conduction defects / arrhythmias
• endocrine / metabolic
  • diabetes mellitus (often early onset)
  • short stature, growth failure

Histology

• muscle biopsy classically shows 'red, ragged fibres' due to increased number of mitochondria

Examples include:

• Leber's optic atrophy
  • symptoms typically develop at around the age of 30 years
  • central scotoma → loss of colour vision → rapid onset of significant visual impairment
• MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes