Clinical Reasoning: A 31-Year-Old Man With Sequential Vision Loss

Abstract

A 31-year-old healthy white male experienced painless sequential vision loss. Brain imaging and laboratory investigations for infectious, inflammatory, and nutritional conditions, in addition to targeted genetic testing for Leber hereditary optic neuropathy (LHON), were all normal or negative. Despite systemic corticosteroid therapy and plasma exchange, vision continued to worsen. Eventually, mitochondrial whole genome sequencing was performed, which demonstrated a mutation at the 13513G>A position confirming the diagnosis of LHON. Three primary mutations (11778G>A, 14484T>C and 3460G>A) account for 90% of LHON cases, therefore it is important to consider whole genome mitochondrial sequencing in cases with a high index of clinical suspicion.

Leber hereditary optic neuropathy: new and emerging therapies

“…Experts suggest testing initially for the three primary mutations. If results for these mutations are negative, screening for the whole mtDNA genome is suggested [11]. Moreover, because patients may harbor an nDNA mutation, further sequencing of autosomal mitochondrial genes should be performed in patients with high clinical suspicion of LHON and negative whole genome mtDNA sequencing [5].…”