Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.