Evaluation of bilateral undefined optic neuropathy based on mitochondrial genetics

Abstract

To assess exogenous environmental factors affecting the phenotypic expression of Leber's hereditary optic neuropathy (LHON), the authors divided 18 cases of bilateral optic neuropathy into two groups with or without mitochondrial (mt) DNA mutations specific for LHON and compared the ocular and other clinical findings and serum concentrations of B group vitamins between the two groups. Ten cases of defined unilateral optic atrophy were also enrolled as control. Of the 18 cases of bilateral optic neuropathy, nine had a G-to-A point mutation at nucleotide position (np) 11778 and one had the mutation at np 3460 of mtDNA. The levels of various B group vitamins were reduced in four of the 10 cases with the mtDNA mutations, three of whom were tobacco and alcohol abusers, indicating not a few numbers of the occult existence of LHON patients in so-called tobacco-alcohol amblyopia patients. Flavin mononucleotide (FMN), one of the activated forms of vitamin B2 and a co-factor of NADH dehydrogenase, was reduced in eight of the ten LHON cases and four of the eight cases of undefined bilateral optic neuropathy without the mtDNA mutations tested, but not in the unilateral cases. Since FMN serves as an electron acceptor from NADH in NADH dehydrogenase, whose function is thought to be damaged due to the mtDNA mutations, FMN may be overconsumed in the LHON patients to maintain visual function. Malnutrition may be a common risk factor of LHON and bilateral optic neuropathy of other etiologies.

Key Words:

• Flavin mononucleotide
• Leber's hereditary optic neuropathy
• mitochondrial DNA mutations
• tobacco-alcohol amblyopia
• vitamin deficiency