From the Guidelines
NARP (Neuropathy, Ataxia, and Retinitis Pigmentosa) mitochondrial disorder is a rare genetic condition caused by mutations in the mitochondrial DNA, specifically in the MT-ATP6 gene, leading to impaired energy production and a range of neurological symptoms. This disorder affects the energy-producing structures within cells, resulting in muscle weakness (neuropathy), coordination problems (ataxia), and vision loss due to retinal degeneration (retinitis pigmentosa) [ 1 ]. The diagnosis and interpretation of mitochondrial variants, such as those associated with NARP, require careful consideration of heteroplasmy, homoplasmy, and the use of resources like MitoMap [ 1 ].
Key Characteristics of NARP
- Rare genetic condition caused by mutations in the mitochondrial DNA
- Impaired energy production leading to neurological symptoms
- Muscle weakness (neuropathy)
- Coordination problems (ataxia)
- Vision loss due to retinal degeneration (retinitis pigmentosa)
Management and Treatment
Treatment for NARP syndrome focuses on symptom management, with a combination of physical therapy, occupational therapy, and regular ophthalmological care. Some physicians prescribe coenzyme Q10, L-carnitine, and other mitochondrial cofactors, although evidence for their effectiveness is limited [ 1 ]. A ketogenic diet may help some patients by providing alternative energy sources for affected cells. Genetic counseling is essential for affected families since this disorder is maternally inherited. Regular monitoring by a multidisciplinary team, including neurologists, ophthalmologists, and metabolic specialists, is crucial for optimal management of this progressive condition [ 1 ].
Important Considerations
- Heteroplasmy and homoplasmy should be reported along with an estimate of heteroplasmy of the variant
- MitoMap is a valuable resource for interpreting mitochondrial variants
- Genetic counseling is essential for affected families
- Regular monitoring by a multidisciplinary team is crucial for optimal management
From the Research
Definition and Characteristics of NARP
- Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) is a syndromic mitochondrial disorder caused by pathogenic variants in MT-ATP6 2.
- The canonical phenotypic features of NARP syndrome include proximal muscle weakness, axonal neuropathy, cerebellar ataxia, and retinitis pigmentosa 2.
- 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 2.
Genetic Aspects of NARP
- NARP is a rare, syndromic, monogenic mitochondrial disorder due to pathogenic variants in MT-ATP6 2.
- The most common variant responsible for NARP is the transversion m.8993T>G 2, 3.
- Most pathogenic MT-ATP6 variants are missense, but a few truncating pathogenic variants have been reported 2.
Diagnosis and Treatment of NARP
- NARP should be suspected if there is a combination of neurological and non-neurological abnormalities 4.
- Genetic testing should be guided by the phenotype, the biopsy findings, and the biochemical results 4.
- Only symptomatic treatment for NARP syndrome is available, and the outcome is usually fair 2.
- Nutritional support may play a crucial role in the management of mitochondrial diseases, including NARP 5.
Reproductive Options and Genetic Counseling
- The provision of accurate genetic counseling and reproductive options to families with NARP is complicated by the unique genetic features of mtDNA 6.
- Reproductive options for prevention of transmission of mtDNA mutations include the use of donor oocytes, prenatal diagnosis, and preimplantation genetic diagnosis 6.