Neuropathy, Ataxia, and Retinitis Pigmentosa Syndrome.

OBJECTIVES

To provide an overview about the phenotype, genotype, treatment, and outcome of neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome.

METHODS

Systematic review by application of appropriate search terms.

RESULTS

NARP syndrome is a syndromic mitochondrial disorder due to pathogenic variants in MT-ATP6. The canonical phenotypic features of NARP syndrome include proximal muscle weakness, axonal neuropathy, cerebellar ataxia, and retinitis pigmentosa. Noncanonical phenotypic features in NARP include epilepsy, cerebral or cerebellar atrophy, optic atrophy, cognitive impairment, dementia, sleep apnea syndrome, hearing impairment, renal insufficiency, and diabetes. So far, 10 pathogenic variants in MT-ATP6 have been associated with NARP, NARP-like syndrome, or NARP/maternally inherited Leigh overlap syndrome. Most pathogenic MT-ATP6 variants are missense, but a few truncating pathogenic variants have been reported. The most common variant responsible for NARP is the transversion m.8993T>G. Only symptomatic treatment for NARP syndrome is available. In most of the cases, patients die prematurely. Patients with late-onset NARP survive longer.

CONCLUSIONS

NARP is a rare, syndromic, monogenic mitochondrial disorder due to pathogenic variants in MT-ATP6. The nervous system and the eyes are most commonly affected. Although only symptomatic treatment is available, the outcome is usually fair.