Genetics · MU Sofia

40. General characteristics of mitochondrial diseases. Leber hereditary optic neuropathy (LHON), MERRF syndrome, MELAS syndrome, NARP syndrome, Leigh syndrome, Kearns-Sayre syndrome.

Covers the general features of mitochondrial diseases, including maternal inheritance, heteroplasmy, the threshold effect and replicative segregation, followed by the pathophysiology and common clinical features. It then goes through Leigh, NARP, LHON, MERRF, MELAS and Kearns-Sayre syndromes, giving each its genetic basis, mechanism and clinical features, with the genes involved named for several of them.

Inside: 7 sections · 11 labelled pictures · 15 flashcards · 5 min

Topic 40 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 7 sections, about 644 words (5 min of reading), with 15 flashcards.

In this note

  1. General characteristics of mitochondrial diseases. Leber hereditary optic neuropathy (LHON), MERRF syndrome, MELAS syndrome, NARP syndrome, Leigh syndrome, Kearns-Sayre syndrome.
  2. II. LEIGH SYNDROME
  3. III. NARP SYNDROME
  4. IV. LEBER HEREDITARY OPTIC NEUROPATHY (LHON)
  5. V. MERRF SYNDROME
  6. VI. MELAS SYNDROME
  7. VII. KEARNS–SAYRE SYNDROME (KSS)

General characteristics of mitochondrial diseases. Leber hereditary optic neuropathy (LHON), MERRF syndrome, MELAS syndrome, NARP syndrome, Leigh syndrome, Kearns-Sayre syndrome.

Mitochondrial diseases are a heterogeneous group of inherited disorders caused by defects in oxidative phosphorylation, leading to impaired ATP production. They predominantly affect high-energy–demand tissues such as the brain, muscles, heart, retina, and endocrine organs.

These diseases can be caused by mutations in:

  • Mitochondrial DNA (mtDNA)
  • Nuclear DNA encoding mitochondrial proteins

Unique Features of Mitochondrial Genetics

1. Maternal Inheritance

  • mtDNA is inherited exclusively from the mother.
  • Affected mothers transmit mutations to all offspring.
  • Affected fathers do not transmit the disease.

2. Heteroplasmy

  • Cells contain a mixture of normal and mutant mtDNA.
  • Proportion of mutant mtDNA varies between tissues.

3. Threshold Effect

  • Clinical disease appears only when mutant mtDNA exceeds a critical threshold in a tissue.
  • Explains variable severity and organ involvement.

4. Replicative Segregation

  • mtDNA is randomly distributed during cell division.
  • Leads to unpredictable disease expression among siblings.

General Pathophysiology

  1. 1. Mutation affects components of the respiratory chain (Complexes I–V).
  2. 2. Reduced electron transport → ↓ ATP production.
  3. 3. Increased reliance on anaerobic glycolysis → lactic acidosis.
  4. 4. Energy failure in high-demand tissues → progressive organ dysfunction.
  5. 5. Oxidative stress and apoptosis contribute to cell loss.

Common Clinical Features of Mitochondrial Diseases

  • Myopathy, muscle weakness
  • Neurological dysfunction (seizures, ataxia, stroke-like episodes)
  • Optic neuropathy, retinopathy
  • Cardiomyopathy
  • Sensorineural hearing loss
  • Endocrine abnormalities (diabetes, growth failure)
  • Lactic acidosis

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