Leber hereditary optic neuropathy (LHON)
Leber Hereditary Optic Neuropathy (LHON) 👁️🧬:
A rare mitochondrial disorder causing painless central vision loss, usually beginning in adolescence or young adulthood.
Typically starts in one eye, progresses to the other within weeks–months, and leads to permanent bilateral visual loss.
ℹ️ About
- LHON: Mitochondrial genetic optic neuropathy → degeneration of retinal ganglion cells.
- Gender: Males more commonly affected (≈80–90%), though females may carry and occasionally manifest the disease.
🧬 Aetiology
- Mutations in mitochondrial DNA (mtDNA), most commonly:
- m.11778G>A
- m.3460G>A
- m.14484T>C
- Disrupts oxidative phosphorylation → impaired ATP production in optic nerve cells.
- Maternal inheritance (mtDNA passed exclusively from the mother).
🩺 Clinical Features
- Subacute, painless central vision loss 🔴.
- Usually one eye first, then the other within weeks–months.
- Optic disc pallor → later bilateral optic atrophy.
- Poor recovery in most cases → lifelong central blindness, peripheral vision preserved.
- “LHON Plus” syndrome: Rare extra-neurological features (ataxia, dystonia, peripheral neuropathy, cardiac conduction defects).
Differentials
- Optic neuritis (e.g. MS-related).
- Toxic optic neuropathies (methanol, ethambutol, tobacco/alcohol amblyopia).
- Other hereditary optic neuropathies (dominant optic atrophy).
- Ischaemic optic neuropathy.
🔎 Investigations
- Genetic Testing: Confirms mtDNA mutation (11778G>A most common, worst prognosis).
- Ophthalmology: Optic disc changes ± retinal nerve fibre layer loss.
- MRI: To exclude compressive/inflammatory optic neuropathy.
💊 Management
- Supportive: Low-vision aids, occupational therapy, psychological support.
- Genetic Counselling: Essential for families - maternal inheritance, variable penetrance.
- Lifestyle: Avoid smoking 🚭 and alcohol 🍷 (mitochondrial stressors).
- Emerging Therapies:
- Idebenone (antioxidant, may improve vision in early disease).
- Gene therapy under trial (allotopic expression of ND4 gene).
References
Revisions
💡 Exam Pearls
- Painless, subacute, central vision loss in a young man = suspect LHON.
- Maternal inheritance but male predominance due to penetrance differences.
- 11778 mutation = worst prognosis; 14484 = best recovery chance.
