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PubMed This is a summary of 14 peer-reviewed journal articles Updated
Neurology

Symptoms and Progression: Navigating the NARP Journey

At a Glance

NARP syndrome is a mitochondrial disorder characterized by three core symptoms: neuropathy (nerve damage), ataxia (balance issues), and retinitis pigmentosa (vision loss). Symptoms vary widely, even within families, and can also include muscle weakness, seizures, and hearing loss.

NARP syndrome is a multisystem condition, meaning it can affect several different parts of the body at the same time [1]. While the name highlights three main areas—nerves, balance, and eyes—the reality of the condition often involves a broader range of symptoms that can change over time.

The Core Triad

The “classic” symptoms that define NARP often appear in early childhood or young adulthood [1][2].

  • Neuropathy (Nerve Damage): This often starts as “pins and needles,” numbness, or pain in the hands and feet. It can also lead to muscle weakness because the nerves are not sending strong signals to the muscles [3].
  • Ataxia (Coordination Issues): Ataxia affects balance and movement. It may look like clumsiness, a shaky gait (way of walking), or difficulty with fine motor tasks like buttoning a shirt [1][4].
  • Retinitis Pigmentosa (Vision Loss): This is a progressive breakdown of the retina. It usually begins with “night blindness” (difficulty seeing in low light) and a loss of peripheral (side) vision, which can eventually lead to “tunnel vision” [3][5].

Beyond the Triad: Secondary Symptoms

Because mitochondria provide energy to the entire body, other systems can also be affected.

  • Developmental and Learning Challenges: Many individuals may experience learning disabilities or delays in reaching developmental milestones [3][6].
  • Seizures: Some patients develop epilepsy or occasional seizures due to the energy shortage in the brain [7].
  • Muscle Weakness: Beyond the weakness caused by nerve damage, the muscles themselves may struggle to function without enough energy [3][8].
  • Hearing Loss: Mitochondrial issues can affect the delicate parts of the inner ear, leading to progressive hearing loss [1].
  • Organ Involvement: In rare cases, mitochondrial diseases can affect the kidneys (such as causing mild protein in the urine) or the heart [9]. While severe kidney issues like End-Stage Renal Disease occur in other mitochondrial disorders, they are exceptionally rare in classic NARP [10]. Early monitoring helps catch these rare events early.

Why NARP is Often Misdiagnosed

Because NARP is rare and its symptoms appear in other diseases, it is frequently confused with more common conditions.

  • Usher Syndrome: Like NARP, Usher syndrome causes vision loss. However, Usher almost always involves significant hearing loss from birth or early childhood, which is less common in NARP [11].
  • Charcot-Marie-Tooth (CMT): Some NARP patients have neuropathy symptoms so similar to CMT that they are misdiagnosed for years [12].
  • Refsum Disease: This metabolic disorder also causes vision loss and ataxia, but doctors can rule it out with a simple blood test for phytanic acid [13].

A Note on Variability

One of the most confusing aspects of NARP is how much it varies—even between members of the same family who have the exact same genetic mutation [14]. This is due to a phenomenon called heteroplasmy, which is covered deeply in The Biology of NARP.

Return to Home

Common questions in this guide

What are the primary symptoms of NARP syndrome?
The core triad of symptoms includes neuropathy (nerve damage causing pain and numbness), ataxia (coordination and balance problems), and retinitis pigmentosa (progressive vision loss starting with night blindness).
Can NARP syndrome affect other parts of the body besides nerves and eyes?
Yes, because mitochondria provide energy to the entire body, the condition can also cause learning challenges, seizures, muscle weakness, hearing loss, and occasionally kidney or heart issues.
Why is NARP syndrome frequently misdiagnosed?
Because NARP is rare, its symptoms can look very similar to more common conditions. For example, vision and hearing changes can resemble Usher syndrome, while the nerve damage can look like Charcot-Marie-Tooth (CMT) disease.
Why do symptoms vary so much between family members with NARP?
Clinical variability is very common in NARP, even within the same family. This happens due to a phenomenon called heteroplasmy, which affects the amount of mutated mitochondrial DNA present in different cells of the body.
How often should someone with NARP be screened for new symptoms?
Regular screening is important because secondary symptoms, such as hearing loss or kidney issues, can develop over time. Your doctor will recommend a specific monitoring schedule based on your current symptoms and genetic mutation.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my current symptoms, where do I fall on the clinical spectrum of NARP?
  2. 2.How often should we screen for secondary symptoms like kidney issues or hearing loss?
  3. 3.Given the clinical variability in our family, what does the 'natural history' usually look like for someone with my specific mutation?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (14)
  1. 1

    Neuropathy, Ataxia, and Retinitis Pigmentosa Syndrome.

    Finsterer J

    Journal of clinical neuromuscular disease 2023; (24(3)):140-146 doi:10.1097/CND.0000000000000422.

    PMID: 36809201
  2. 2

    Delineating MT-ATP6-associated disease: From isolated neuropathy to early onset neurodegeneration.

    Stendel C, Neuhofer C, Floride E, et al.

    Neurology. Genetics 2020; (6(1)):e393 doi:10.1212/NXG.0000000000000393.

    PMID: 32042921
  3. 3

    Extending the phenotype of posterior column ataxia with retinitis pigmentosa caused by variants in FLVCR1.

    Vaughan DP, Costello DJ

    American journal of medical genetics. Part A 2022; (188(4)):1259-1262 doi:10.1002/ajmg.a.62612.

    PMID: 34931442
  4. 4

    "Hole" Exome Sequences: The Importance of Phenotyping to Fill the Gaps in Whole Exome Sequencing.

    McNamara RC, Zven S, Horvat DE, et al.

    Pediatric neurology 2024; (152()):1-3 doi:10.1016/j.pediatrneurol.2023.11.017.

    PMID: 38168579
  5. 5

    Epilepsy in MT-ATP6 - related mils/NARP: correlation of elettroclinical features with heteroplasmy.

    Licchetta L, Ferri L, La Morgia C, et al.

    Annals of clinical and translational neurology 2021; (8(3)):704-710 doi:10.1002/acn3.51259.

    PMID: 33476484
  6. 6

    Phenotypic and genotypic peculiarities in Chinese patients with Leigh syndrome.

    Finsterer J

    Chinese medical journal 2019; (132(5)):626-629 doi:10.1097/CM9.0000000000000090.

    PMID: 30807363
  7. 7

    Phenotypic spectrum of maternally inherited Leigh Syndrome associated with the m.8993T>G variant.

    Gropman A, Chiaramello A

    Molecular genetics and metabolism reports 2018; (15()):134 doi:10.1016/j.ymgmr.2018.04.004.

    PMID: 30023306
  8. 8

    X-linked Myotubular Myopathy Manifesting Carrier with Central and Peripheral Nervous System Involvement.

    Takeuchi Y, Masuda T, Kimura N, et al.

    Internal medicine (Tokyo, Japan) 2024; (63(24)):3371-3375 doi:10.2169/internalmedicine.3417-23.

    PMID: 38631855
  9. 9

    Renal Involvement in Neuropathy, Ataxia, Retinitis Pigmentosa (NARP) Syndrome: A Case Report.

    Lemoine S, Panaye M, Rabeyrin M, et al.

    American journal of kidney diseases : the official journal of the National Kidney Foundation 2018; (71(5)):754-757 doi:10.1053/j.ajkd.2017.09.020.

    PMID: 29224958
  10. 10

    Expanding the molecular and phenotypic spectrum of truncating MT-ATP6 mutations.

    Bugiardini E, Bottani E, Marchet S, et al.

    Neurology. Genetics 2020; (6(1)):e381 doi:10.1212/NXG.0000000000000381.

    PMID: 32042910
  11. 11

    The first deaf-blind patient in Russia with Argus II retinal prosthesis system: what he sees and why.

    Demchinsky AM, Shaimov TB, Goranskaya DN, et al.

    Journal of neural engineering 2019; (16(2)):025002 doi:10.1088/1741-2552/aafc76.

    PMID: 30620937
  12. 12

    Cerebellar Bottom of Fissure Hyperintensities in MT-ATP6-Associated Ataxia.

    Roeben B, Bültmann E, Stendel C, Synofzik M

    Annals of neurology 2022; (91(3)):438-440 doi:10.1002/ana.26311.

    PMID: 35094430
  13. 13

    Ophthalmic Diagnosis and Novel Management of Infantile Refsum Disease with Combination Docosahexaenoic Acid and Cholic Acid.

    Elghawy O, Zhang AY, Duong R, et al.

    Case reports in ophthalmological medicine 2021; (2021()):1345937 doi:10.1155/2021/1345937.

    PMID: 34664020
  14. 14

    Pathogenic variants in MT-ATP6: A United Kingdom-based mitochondrial disease cohort study.

    Ng YS, Martikainen MH, Gorman GS, et al.

    Annals of neurology 2019; (86(2)):310-315 doi:10.1002/ana.25525.

    PMID: 31187502

This page provides educational information about NARP syndrome symptoms and progression. Always consult your neurologist or geneticist for personalized medical advice and ongoing symptom monitoring.

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