NARP (neuropathy, ataxia, retinitis pigmentosa)
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A young adult with developmental delay has progressive ataxia, peripheral neuropathy, and night blindness. Retinitis pigmentosa is found on fundoscopy.
Maternal (mtDNA); MT-ATP6 m.8993T>G or T>C
- Same gene as some Leigh syndrome cases
- Higher mutant load (>90%) → Leigh syndrome
- Lower mutant load (70-90%) → NARP
- Peripheral neuropathy (sensory)
- Cerebellar ataxia
- Retinitis pigmentosa
- Developmental delay/cognitive impairment
- Proximal muscle weakness
- Seizures (some)
- Overlaps with Leigh syndrome at high heteroplasmy
- Targeted mtDNA testing for MT-ATP6 m.8993T>G or T>C, with heteroplasmy quantification (severity tracks mutant load)
- Fundoscopy confirms retinitis pigmentosa; brain MRI may show cerebellar/brainstem changes
- Unlike many mitochondrial disorders, muscle biopsy typically does not show ragged red fibers
- Largely supportive (no disease-modifying therapy): low-vision support, physical therapy for ataxia, anticonvulsants for seizures
- Maternally inherited (mtDNA): all offspring of an affected mother are at risk, and heteroplasmy makes recurrence severity unpredictable
NARP = the diagnosis: the name itself is the mnemonic: Neuropathy, Ataxia, Retinitis Pigmentosa. All three cardinal features are in the name.
Same gene, different load: MT-ATP6 mutations at m.8993 show lower heteroplasmy (70-90%) causing NARP, while higher mutant load (>90%) causes the more severe Leigh syndrome.