Neuron Specific Enolase: A Potential Serological Marker for Predicting Phenotypic Expression in Carriers and Affected Patients With Leber's Hereditary Optic Neuropathy

Abstract

Purpose:: Neuron Specific Enolase (NSE) is a serological marker that reflects neuronal distress. This study was to investigate NSE as a possible laboratory measure of Leber's Hereditary Optic Neuropathy expression and compare it in regards to age, gender, disease status, and predictive value in anticipating conversion from a Carrier of the mitochondrial mutation to full disease (Affected).

Methods:: Human blood samples were collected in Brazil from 45 Carriers (mean age: 36.2 ±18.1 years, 17 males and 28 females) and 14 Affected individuals (mean age: 42.9± 14.1 years, 13 males and 1 female) belonging to a large pedigree with the 11778/ND4 LHON haplogroup J mitochondrial DNA (mtDNA) point mutation. Immediately after venipuncture, clotted blood was centrifuged at 1,000 rpm for 15 minutes, serum samples were carefully aliquoted into labeled vials, and initially stored at -20°C. Serum samples were immediately shipped on dry ice to the United States (Doheny Eye Institute), and stored at -86°C prior to analysis for NSE levels using a commercially available NSE Enzyme Immunosorbent Assay kit (ALPCO Diagnostics, Windham, NH).

Results:: 93% of the Affected were males compared to 38% of the Carrier subjects (p<0.001). Age was negatively correlated with NSE in the carrier group (p<0.001) but not in the affected group. NSE was stratified by age to separate out Carriers at risk from those having successfully prevented conversion (<40 and 40+ years). Carriers 40+ had lower NSE levels than Affected 40+ individuals (p=0.06).

Conclusions:: Though the sample size was small, it is interesting that NSE levels were higher in Affected subjects compared to age-matched Carriers and that older Carriers had lower levels than those still at risk for conversion. This provides further evidence that some individuals, with gender bias, compensate for the mtDNA mutation more successfully. Conversely, higher NSE levels may predict conversion of Carriers to Affected in LHON.

Keywords: enzymes/enzyme inhibitors • mitochondria • neuro-ophthalmology: optic nerve