Nationwide epidemiological survey of Leber hereditary optic neuropathy in Japan

Abstract

Background: Leber hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy that leads to central loss of vision, predominantly in young males. Most LHON cases have one of three primary point mutations in mitochondrial DNA (mtDNA). The annual incidence and prevalence of LHON in Japan are not known. Thus, we estimated the annual incidence of molecularly confirmed LHON in Japan during 2014.

Methods: Sequential questionnaires were sent to 1397 facilities, which included all of the university hospitals in Japan, and they were certified by either the Japanese Ophthalmological Society or the Japanese Neuro-Ophthalmological Society. We calculated the incidence number (I_r) as the number of patients who developed LHON in 2014 and its 95% confidence interval.

Results: We received 861 responses to the first questionnaire, where 49 facilities reported 72 cases (67 were male and 5 were female) of newly developed LHON during 2014. I_r was calculated as 117, and the 95% confidence interval ranged from 81 to 153. For the second questionnaire, responses were received from 30 facilities, where the median age at onset was 38 years for males and 30 years for females, and 86.5% of cases possessed the mtDNA ND4/G11778A mutation.

Conclusion: Approximately 120 cases of newly developed LHON were reported during 2014 in Japan, and 93.2% were males.

Keywords: Annual incidence; Gender proportion; Leber hereditary optic neuropathy; Mitochondrial DNA; Penetrance.

Fig. 1

Distribution of age at onset for 44 patients with newly developed Leber hereditary optic neuropathy (LHON) in Japan during 2014. The histogram was generated based on the 30 responses obtained from 49 facilities that reported one or more new patients with LHON in the first questionnaire and that received the second questionnaire. Closed columns indicate male patients and hatched columns indicate female patients.