Leber’s Hereditary Optic Neuropathy with Mitochondrial DNA Mutation G11778A: A Systematic Literature Review and Meta‐Analysis

Abstract

Background. LHON is a progressive disease with early disease onset and male predominance, usually causing devastating visual loss to patients. These systematic review and meta-analysis are aimed at summarizing epidemiology, disease onset and progression, visual recovery, risk factors, and treatment options of Leber’s hereditary optic neuropathy (LHON) with mitochondrial DNA mutation G11778A from current evidence. Methods. The PubMed database was examined from its inception date to November 2021. Data from included studies were pooled with either a fixed-effects model or a random-effects model, depending on the results of heterogeneity tests. Sensitivity analysis was conducted to test the robustness of results. Results. A total of 41 articles were included in the systematic review for qualitative analysis, and 34 articles were included for quantitative meta-analysis. The pooled estimate of proportion of G11778A mutation among the three primary mutations of mitochondrial DNA (G11778A, G3460A, and T14484C) for LHON was 73% (95% CI: 67% and 79%), and the LHON patients with G11778A mutation included the pooled male ratio estimate of 77% (76% and 79%), the pooled age estimate of 35.3 years (33.2 years and 37.3 years), the pooled onset age estimate of 22.1 years (19.7 years and 24.6 years), the pooled visual acuity estimate of 1.4 LogMAR (1.2 LogMAR and 1.6 LogMAR), and the pooled estimate of spontaneous visual recovery rate (in either 1 eye) of 20% (15% and 27%). Conclusions. The G11778A mutation is a prevalent mitochondrial DNA mutation accounting for over half of LHON cases with three primary mutations. Spontaneous visual recovery is rare, and no effective treatment is currently available.

Prevalence of Leber hereditary optic neuropathy in the Community of Madrid (Spain), estimation with a capture-recapture method

“…Leber hereditary optic neuropathy (LHON) is among the most common inherited mitochondrial diseases [ 1 ] and was the first to be associated with a primary mutation in mitochondrial DNA (mtDNA) [ 2 ]. Clasically three primary pathogenic point mitochondrial DNA mutations: G11778A, G3460A, and T14484C have been considered to be responsible for 90% of LHON cases [ 3 ]. Nevertheless in the last years the spectrum of the disease has been widened, as cases with no mitocondrial inheritance have been described, showing a greater genetic heterogeneity of nuclear LHON-like phenotypes [ 4 – 6 ].…”

“…LHON typically presents in young adults as bilateral painless subacute visual loss [ 3 ]. The diagnosis of this neuropathy should be based on a careful history and evaluation of key structural and functional visual parameters.…”