A 40-year-old woman presents with progressive bilateral visual loss, optic disc pallor, and visual field showing cecocentral scotomas bilaterally. MRI brain and orbits are normal. Mitochondrial DNA analysis reveals the 11778 G>A mutation in the ND4 gene. Which subunit of the mitochondrial complex is affected in this condition?

• A Complex II (Succinate dehydrogenase) — SDHB subunit
• B Complex I (NADH ubiquinone oxidoreductase) — ND4 subunit ✓
• C Complex III (Ubiquinol cytochrome c oxidoreductase) — cytochrome b subunit
• D Complex IV (Cytochrome c oxidase) — COX1 subunit

Explanation

Leber hereditary optic neuropathy (LHON) is caused by mitochondrial DNA point mutations affecting subunits of Complex I (NADH:ubiquinone oxidoreductase). The three primary mutations are: 11778 G>A in ND4 gene (most common, ~70% of cases), 3460 G>A in ND1, and 14484 T>C in ND6. These mutations impair electron transport chain Complex I function, reducing mitochondrial ATP production and increasing reactive oxygen species, selectively affecting the small-caliber retinal ganglion cell axons in the papillomacular bundle (explaining cecocentral scotoma).

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.