Neuropathy, ataxia, and retinitis pigmentosa

Definition

Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome is a clinically heterogeneous condition often characterized by a combination of sensory-motor neuropathy, cerebellar ataxia, and night blindness. Its prevalence is estimated at 1 in 12 000. NARP usually manifests in young adults. Clinical presentation includes a combination of the following symptoms: early salt and pepper retinopathy; retinitis pigmentosa; sluggish pupils; nystagmus; blindness; developmental delay; corticospinal tract atrophy; dementia; hearing loss; seizures; ataxia; sensory neuropathy and proximal neurogenic muscle weakness. NARP syndrome is a maternally inherited condition associated with a 8993T>G mutation in the mtDNA gene, MTATP6, coding for the subunit ATPase 6. The 8993T>G mutation results in an amino acid change from a highly conserved leucine 156 to arginine (L156R) and leads to a severe impairment of the synthesis of mitochondrial ATP, reducing cellular energy and resulting in cell death, particularly in tissues highly dependent upon oxidative phosphorylation metabolism, such as the brain and retina. This mutation is also present in 8-10% of patients with Leigh disease. These cases are conventionally defined as maternally-inherited Leigh syndrome (MILS). MILS is the most severe form of NARP syndrome and usually manifests in subsequent affected generations (pseudo-anticipation). Treatment is only supportive. However, recent in vitro studies have suggested that antioxidants may be a useful form of treatment.

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