CHILDHOOD LEBER HEREDITARY OPTIC NEUROPATHY (ND1 3460) WITH VISUAL RECOVERY/

The authors report the clinical features and the results of genetic an d biochemical studies of a child affected by ND1/3460 Leber's heredita ry optic neuropathy, who demonstrates a persistent visual recovery aft er protracted monitoring, A 10-year-old male suffered from a severe ri ght visual impairment that was incidentally detected. Within 2 months the left eye was also seriously involved, and visual acuity worsened t o 20/300 in both eyes, associated with bilateral cecocentral scotomas and dyschromatopsia. During the following months a progressive visual improvement occurred, and 2 years later the visual acuity was 20/20 OU , After 9 years of follow-up the clinical status is unchanged. The mut ation at np ND1/3460 was found to be virtually homoplasmic in the prob and's mtDNA, which was extracted either from platelets or leukocytes, whereas the mother and the sister tested heteroplasmic for the same mu tation. The specific activity of complex I in platelets was reduced in the proband and normal in his relatives. An abnormal resistance of NA DH:ubiquinone reductase to the inhibitory effect of rotenone was found in platelet mitochondria from the proband and family members and was consistent with the degree of heteroplasmy. This pattern of biochemica l abnormalities suggests a cumulative effect of the increasing percent age of mutated mtDNA on complex I function, which involves the interac tion between complex I and its substrate ubiquinone in the heteroplasm ic condition (asymptomatic state), and the catalytic function of compl ex I, as mutated mDNA turns toward the homoplasmic condition (symptoma tic state). (C) 1998 by Elsevier Science Inc. All rights reserved.