mtDNAassociated Leigh syndrome affects the brain of afflicte

mtDNA-associated Leigh syndrome affects the brain of afflicted individuals and has an infantile onset. NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) has less severe symptoms with an onset in childhood. The same mtDNA mutation can cause both of these diseases. How can these differences in disease presentation, severity, and age of onset be explained for these two diseases?

Solution

Leigh syndrome (or subacute necrotizing encephalomyelopathy) is characterized by onset of symptoms typically between age three and 12 months, often following a viral infection. Decompensation (often with elevated lactate levels in blood and/or CSF) during an intercurrent illness is typically associated with psychomotor retardation or regression. Neurologic features include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy. Extraneurologic manifestations may include hypertrophic cardiomyopathy. About 50% of affected individuals die by age three years, most often as a result of respiratory or cardiac failure. NARP is characterized by proximal neurogenic muscle weakness with sensory neuropathy, ataxia, and pigmentary retinopathy. Onset of symptoms, particularly ataxia and learning difficulties, is often in early childhood. Individuals with NARP can be relatively stable for many years, but may suffer episodic deterioration, often in association with viral illnesses.