NARP syndrome

NARP syndrome (Neuropathy, Ataxia, and Retinitis Pigmentosa) is a rare mitochondrial disorder caused by pathogenic variants in the MT-ATP6 gene, which encodes a subunit of mitochondrial ATP synthase (complex V). The condition is characterized by a triad of sensory or sensorimotor neuropathy, cerebellar ataxia, and retinitis pigmentosa (progressive degeneration of the retina). NARP syndrome is part of a clinical spectrum that also includes maternally inherited Leigh syndrome (MILS), with the severity largely determined by the heteroplasmy level of the mitochondrial DNA mutation, most commonly the m.8993T>G or m.8993T>C variant. When the mutation load is typically between 70% and 90%, the NARP phenotype predominates, whereas higher mutation loads (above 90%) are more commonly associated with the more severe Leigh syndrome. The disease primarily affects the nervous system and the eyes. Additional clinical features may include learning difficulties, developmental delay, seizures, dementia, proximal muscle weakness, and hearing loss. Cardiac conduction defects and short stature have also been reported in some patients. Symptoms typically emerge in childhood or young adulthood, though the age of onset and severity can vary considerably even within the same family due to differences in mitochondrial mutation load across tissues. There is currently no cure for NARP syndrome. Treatment is supportive and symptomatic, focusing on management of neurological symptoms, seizure control with appropriate anticonvulsants, physical and occupational therapy for ataxia and neuropathy, and ophthalmological monitoring for retinitis pigmentosa. Nutritional supplementation with coenzyme Q10, B vitamins, and other mitochondrial cofactors has been tried, though evidence for efficacy remains limited. Genetic counseling is important for affected families, particularly regarding the complexities of mitochondrial inheritance and the unpredictable nature of heteroplasmy transmission from mother to offspring.

Common questions about NARP syndrome