OMIM ID:
Neuropathy, Ataxia, and Retinitis Pigmentosa
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Night blindness and visual field restriction are early symptoms usually in the second decade of life. The retina may first show a salt-and-pepper pigmentary pattern which later resembles the classic bone-spicule pattern of retinitis pigmentosa with vascular attenuation. The optic nerve becomes pale and eventually marked optic atrophy develops. Severe vision loss is evident in young adults and some patients become blind.
Systemic Features
The onset of systemic symptoms such as unsteadiness occurs some time in the second decade of life. Irritability, delayed development, and psychomotor retardation may be evident in children whereas older individuals can have frank dementia. The MRI may reveal cerebral and cerebellar atrophy. Seizures may have their onset by the third decade. Numbness, tingling and pain in the extremities are common. EMG and nerve conduction studies can demonstrate a peripheral neuropathy. Neurogenic muscle weakness can be marked and muscle biopsy may show partial denervation. Some patients have hearing loss. A few patients have cardiac conduction defects.
Genetics
Inheritance
This is a mitochondrial disorder with pedigrees showing maternal transmission. Mutations (8993T-G) have been found in subunits of mitochondrial H(+)-ATPase or MTATP6. The amount of heteroplasmy is variable and likely responsible for the clinical heterogeneity in this disorder. Individuals with more than 90% mutated chromosomes are considered to have a subtype of Leigh syndrome (MILS) with earlier onset (3-12 months of age). NARP patients usually have 70-80% or less of mutated mitochondria. The amount of heteroplasmy may vary among tissues.