Leber¿s hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients (Orphanet Journal of Rare Diseases)

Background: Leber?s hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. Here we describe the clinical and molecular characteristics of 20 patients with disease onset after the age of 50?years (late onset-LHON). Methods: From a cohort of 251 affected and 277 unaffected LHON carriers, we identified 20 patients with onset of visual loss after the age of 50?years. Using structured questionnaires, data including basic demographic details, age of onset, progression of visual loss and severity as well as exposure to possible environmental triggers including alcohol, smoking and illicit drugs were retrospectively collected. Groups were compared using the Mann?Whitney-U-Test for two independent groups of sampled data. Results: The proportion of late onset-LHON in our cohort was 8% (20 patients, 15 males, 5 females). The mtDNA mutations m.11778G?>?A and m.3460G?>?A were found in 16 and 4 patients, respectively. Among 89 asymptomatic carriers above the age of 50?years (28 males, 61 females), the mtDNA mutations m.11778G?>?A, m.3460G?>?A and m.14484?T?>?C were found in 60, 12 and 17 carriers, respectively. Late onset-LHON patients had significantly higher mean cumulative tobacco and alcohol consumption compared with unaffected carriers. However, there was no significant difference between late onset- and typical LHON patients with regard to daily tobacco and weekly alcohol consumption before disease onset. Conclusion: As already shown for typical LHON, alcohol consumption and smoking are important trigger factors also for the late manifestation. LHON should be considered in the differential diagnosis of subacute blindness even in older patients.