Abstract Body:

Purpose: With promising clinical trials, there is a need for an accurate understanding of the epidemiology of LHON. This study aims to estimate the prevalence and describe the clinical presentation of LHON in British Columbia, Canada.

Study Design: In British Columbia, all clinical genetic analyses are co-ordinated and documented through the Provincial Genetics Laboratory. In a retrospective study, all subjects diagnosed with LHON between 1996 - 2016 were collated and clinical information was gathered.

Methods: Chart review of all patients with a mitochondrial sequencing diagnosis consistent with LHON were reviewed and their clinical data were gathered.

Results: We identified 44 subjects with genetically-confirmed LHON. In the mid-year point of the study, there were 3,444,285 people <65 years old. The minimum point prevalence for LHON within this population was 1.28 per 100,000 (95% CI 1.12-1.73 per 100,000). This is lower than seen in England and comparable to prevalence rates in Finland and Denmark. Heteroplasmy was present in 9% of cases. Of the 44 cases, 41 were LHON primary mutations (11778G>A, 14484T>C, and 3460G>A). Overall, subjects were 55% male, with an average age of symptom onset at 27.4 +/- 4.8 years. For those with symptomatic vision loss, the average time between fellow eye involvement was 2.7 +/- 0.9 months. The average wait time from initial onset of visual loss to diagnostic testing was 1.3 +/- 0.7 years. One patient was treated with idebenone. Clinical phenotype varied: there were 3 patients with MS-like illness with symptomatic white matter lesions, 2 with dystonia and 1 with a cardiac conduction abnormality. Finally, seven subjects experienced partial recovery of visual loss.

Conclusions: Epidemiologic information can help inform the patient population that may benefit from new treatments. In British Columbia, nearly 2 in 50000 people possess LHON mt DNA mutations, although there is a significant delay in diagnosis. Mechanisms to improve the availability of mitochondrial sequencing is an important consideration in future healthcare policies.