Reactive Oxygen Species Causing Gene Mutations Linking Heavy Metal Toxicity to Neurodegeneration

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by combined upper and lower motor neuron loss. While most cases are sporadic, environmental and occupational exposures are increasingly recognized as important disease modifiers.

Case Presentation: A 57-year-old male presented with an insidious onset of asymmetric upper limb weakness, which gradually progressed to involve significant muscle wasting, fasciculations, and early bulbar symptoms. Electromyographic studies demonstrated fasciculations, fibrillations, and neurogenic recruitment patterns, findings consistent with motor neuron disease. The patient had a prolonged occupational history of manual labor at oil production sites, with chronic exposure to heavy metals, and was known to have chronic hepatitis B infection. Despite initiation of riluzole therapy and comprehensive multidisciplinary supportive management, the disease followed a progressive course, culminating in respiratory failure and end-stage disease.

Discussion: This case underscores the potential contribution of chronic heavy metal exposure as a molecular driver in the pathogenesis of amyotrophic lateral sclerosis (ALS). The underlying mechanisms may involve zinc displacement from DNA repair proteins, oxidative DNA damage, mitochondrial dysfunction, disrupted axonal transport, and neuroinflammatory cascades. Additionally, concomitant systemic comorbidities such as chronic hepatitis B infection and prolonged physical strain may have synergistically accelerated neurodegenerative processes, contributing to disease progression.

Conclusion: Environmental and occupational exposure to neurotoxicants may influence the clinical trajectory of amyotrophic lateral sclerosis (ALS) by exacerbating intrinsic neuronal vulnerabilities. Recognition of these pathogenic modifiers is crucial for comprehensive risk assessment, patient counseling, and the formulation of targeted therapeutic strategies, including antioxidant therapy, mitochondrial stabilization, and metal chelation approaches.

KEYWORDS:

Amyotrophic lateral sclerosis, electromyography, heavy metals, occupational exposure, neurodegeneration, oxidative stress.