Mitochondrial diseases

Mitochondrial diseases

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
  Mitochondrial diseases follow a maternal inheritance pattern
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  Importance: 33
• none of the children of an affected male will inherit the disease
  For a man with mitochondrial disease, none of his children will inherit the condition
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  Importance: 51
• 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
  Heteroplasmy is defined as the presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual. It results in variable expression of mitochondrial disease
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  Importance: 36

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
    Lactic acidosis is a common feature of mitochondrial diseases
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    Importance: 95
    (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
  Leber's Hereditary Optic Neuropathy: mitochondrial inheritance pattern
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  Importance: 62
  • symptoms typically develop at around the age of 30 years
  • central scotoma → loss of colour vision → rapid onset of significant visual impairment
    central scotoma → loss of colour vision → rapid onset of significant visual impairment
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• MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
• MERRF syndrome: myoclonus epilepsy with ragged-red fibres
• Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
  Kearns-Sayre syndrome - mitochondrial inheritance - onset < 20-years-old - external ophthalmoplegia - retinitis pigmentosa
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  Importance: 65
• sensorineural hearing loss

+PassMedicine Notes

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
• MERRF syndrome: myoclonus epilepsy with ragged-red fibres
• Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
• sensorineural hearing loss