NDUFV1 mutation presenting as isolated progressive optic neuropathy: a unique manifestation of mitochondrial complex...

Mutations in the NDUFV1 gene, encoding a subunit of mitochondrial complex I, are typically associated with severe neurological disorders such as Leigh syndrome. We report a pre-teen girl with progressive bilateral optic atrophy and steady visual deterioration, without neurological findings or systemic involvement. Neuroimaging was unremarkable for white matter lesions or structural brain lesions. Whole-exome sequencing demonstrated a homozygous missense mutation (c.1156C>T, p. Arg386Cys) in NDUFV1, implying a nuclear-encoded complex I defect. Laboratory analysis revealed increased lactate levels, consistent with mitochondrial dysfunction. Despite treatment with coenzyme Q, riboflavin and idebenone, no significant visual improvement occurred. This case represents a novel phenotype of NDUFV1-associated disease isolated optic atrophy without systemic involvement expanding the clinical spectrum of NDUFV1 mutations. Recognising this unique mitochondrial optic neuropathy may aid early diagnosis and targeted management.