Neuron-specific enolase is elevated in asymptomatic carriers of Leber's hereditary optic neuropathy.

PURPOSE: Neuron-specific enolase (NSE) is a biomarker for neuronal stress. Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease affecting retinal ganglion cells (RGC). These RGCs and their axons in the retinal nerve fiber layer (RNFL) and optic nerve head may show subclinical pathology in unaffected mutation carriers, or undergo cell death in affected patients. We hypothesize that increased levels of blood NSE may characterize LHON carriers as a biomarker of ongoing RGC stress. METHODS: Serum was obtained from 74 members of a Brazilian pedigree with LHON carrying the homoplasmic 11778/ND4 mitochondrial DNA mutation. Classified by symptoms and psychophysical metrics, 46/74 patients were unaffected mutation "carriers," 14/74 were "affected," and 14/74 were "off-pedigree" controls. Serum NSE levels were determined by ELISA specific for the γ subunit of NSE. RESULTS: Serum NSE concentrations in carriers (27.17 ± 39.82 µg/L) were significantly higher than affected (5.66 ± 4.19 µg/L; P = 0.050) and off-pedigree controls (6.20 ± 2.35 µg/L; P = 0.047). Of the 14/46 (30.4 %) carriers with significantly elevated NSE levels (mean = 75.8 ± 42.3 µg/L), 9/14 (64.3%) were male. Furthermore, NSE levels were nearly three times greater in asymptomatic male carriers (40.65 ± 51.21 µg/L) than in asymptomatic female carriers (15.85 ± 22.27 µg/L; P = 0.034). CONCLUSIONS: Serum NSE levels are higher in LHON carriers compared with affected and off-pedigree individuals. A subgroup of mostly male carriers had significantly elevated serum NSE levels. Thus, male carriers are at higher risk for LHON-related neuronal stress.

Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy.

PURPOSE: To report the ophthalmologic characteristics of a newly identified seven-generation pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy consisting of 328 living individuals, 111 of whom are maternally related. DESIGN: Observational population cohort study. METHODS: This prospective study of a large Brazilian Leber hereditary optic neuropathy pedigree was carried out as a field investigation in Brazil. We describe the ophthalmologic findings of 192 eyes from 96 maternally related individuals of this pedigree. Spouses were used as control subjects. We conducted comprehensive neuro-ophthalmologic examinations with psychophysical tests, Humphrey visual fields, and fundus photographs. We also correlated the ophthalmologic findings with the previously published epidemiologic assessment of risk factors. RESULTS: We examined 76 carriers and 20 affected individuals. The affected individuals showed severe disease with a mean visual acuity of 2.04 logarithm of the minimal angle of resolution and without evidence of recovery. All the affected individuals showed diffuse optic atrophy with a cup-to-disk ratio greater than 0.5 in 55% of cases. Moreover, among Affected individuals, smokers had a poorer visual acuity (P =.002). Among carriers there were several subclinical abnormalities, including microangiopathy, swelling of nerve fibers, and visual field abnormalities that did not correlate with tobacco or alcohol consumption. CONCLUSIONS: Our results demonstrate a significant influence of environmental risk factors, particularly smoking, for developing Leber hereditary optic neuropathy and for the severity of its clinical expression. However, smoking did not correlate with the subclinical abnormalities detected in carriers. Moreover, subclinical abnormalities were equally distributed between gender.