Leber's hereditary optic neuropathy (LHON) causes acute/subacute bilateral sequential central visual loss. The most common mitochondrial DNA point mutation responsible is at position:
- A T14484C (ND6 subunit)
- B G3460A (ND1 subunit)
- C G11778A (ND4 subunit) ✓
- D A3243G (tRNA Leu)
Explanation
G11778A mutation in the ND4 subunit of complex I accounts for approximately 50-70% of LHON cases worldwide (>90% in Chinese patients). It has the worst prognosis for visual recovery (<5%). T14484C (ND6) accounts for ~14% and has the best spontaneous recovery (~50%). G3460A (ND1) accounts for ~14%. All three primary mutations affect complex I of the mitochondrial electron transport chain, leading to increased reactive oxygen species and apoptosis of retinal ganglion cells. A3243G causes MELAS syndrome. Idebenone (an antioxidant analog of CoQ10) is FDA/EMA-approved for LHON treatment.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.