Neuropathy, ataxia and retinitis pigmentosa (NARP) syndrome

Keywords Disease name and synonyms Diagnostic criteria/definition Differential diagnosis Etiology Clinical description Diagnostic methods Genetic counseling Prenatal diagnosis Management Unresolved questions References Abstract The syndrome of Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) is clinically heterogeneous but it is often characterized by a combination of sensory-motor neuropathy, cerebellar ataxia, and night blindness. Its prevalence is approximately estimated at 1:12 000. NARP usually presents in young adults. Clinical presentation includes a combination of the following symptoms: early salt and pepper retinopathy; retinitis pigmentosa; sluggish pupils; nystagmus; blindness; proximal muscle weakness; developmental delay; corticospinal tract atrophy; dementia; hearing loss; seizures; ataxia; sensory neuropathy; proximal neurogenic muscle weakness. A maternally inherited condition, the NARP syndrome is associated with the 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 cell death, particularly in tissues highly dependent upon the oxidative phosphorylation metabolism, such as brain and retina. This mutation is also retrieved in 8-10% of Leigh disease, which in this case is conventionally defined with the acronym MILS (maternally-inherited Leigh syndrome). Thus, MILS represents the most severe phenotypic presentation of the NARP syndrome and it usually manifests in subsequent affected generations resembling pseudo-anticipation. Treatment is only supportive. Antioxidants have been recently proposed as helpful on the basis of experimental " in vitro " evidences.