Defining mitochondrial disease
Mitochondrial diseases have progressive and severe impacts on quality of life1-4
There are many types of diseases affecting mitochondria, each characterized by progressively worsening symptoms and involving multiple organs or organ systems.5 They are often fatal. While rare, mitochondrial disease may actually be more common than some think.1,6
Mitochondrial diseases typically manifest as neuromuscular or metabolic conditions7
Parts of the body that require the most energy are often the most affected7
Symptoms may impact the7:
The involvement of multiple organ systems may suggest a mitochondrial disease.5
Genetic testing is often the fastest way to confirm diagnosis.8,9
Symptoms of mitochondrial diseases vary considerably and often mimic other diseases5
The complex presentation is a barrier to diagnosis, often resulting in misdiagnosis or delayed diagnosis.5 However, advancements in genetic testing have made diagnosing mitochondrial diseases easier. If you see red-flag symptoms of mitochondrial diseases, consider conducting a genetic test to help shorten the diagnostic journey.10,11
Red-flag symptoms of mitochondrial diseases1,10
Reduced energy/
fatigueMuscle weakness
Difficulty swallowing or walking
Neurological symptoms (eg, epilepsy, ataxia, hearing loss)
In infants: hypotonia, weakness, failure to thrive, and metabolic acidosis (especially lactic acidosis)
Delayed and incorrect diagnoses are common for patients with mitochondrial diseases5
55%
of patients reported receiving an incorrect nonmitochondrial disease diagnosis.
32%
of those patients received multiple misdiagnoses of nonmitochondrial diseases.
Historically, the diagnostic journey has been lengthy and required many tests before a conclusion was made.5
Now, genetic testing provides the most direct path to diagnosis, as long as the test is inclusive of genes involved in mitochondrial function. If patients experience mitochondrial disease symptoms and have undergone prior tests that did not include genes involved in mitochondrial function, it's important to retest or reanalyze the sample.11
- Wang J, El-Hattab AW, Wong LJC. TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews®. [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.
- Cohen B, Balcells C, Hotchkiss B, et al. A retrospective analysis of health care utilization for patients with mitochondrial disease in the United States: 2008-2015. Orphanet J Rare Dis. 2018;13(1):210. doi:10.1186/s13023-018-0949-5
- Elson JL, Cadogan M, Apabhai S, et al. Initial development and validation of a mitochondrial disease quality of life scale. Neuromuscul Disord. 2013;23(4):324-329. doi:10.1016/j.nmd.2012.12.012
- Orsucci D, Calsolaro V, Siciliano G, Mancuso M. Quality of life in adult patients with mitochondrial myopathy. Neuroepidemiology. 2012;38:194-195. doi:10.1159/000337161
- Grier J, Hirano M, Karaa A, et al. Diagnostic odyssey of patients with mitochondrial disease: results of a survey. Neurol Genet. 2018;4(2):e230. doi:10.1212/NXG.0000000000000230
- Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753–759. doi:10.1002/ana.24362
- Parikh S, Goldstein A, Karaa A, et al. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017;19(12):10.1038/gim.2017.107. doi:10.1038/gim.2017.107
- Parikh S, Goldstein A, Koenig MK, et al. Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2015;17(9):689–701. doi:10.1038/gim.2014.177
- Thymidine kinase 2 deficiency. National Organization for Rare Disorders. Updated March 4, 2025. Accessed March 25, 2025. https://rarediseases.org/rare-diseases/thymidine-kinase-2-deficiency/
- Conti F, Di Martino S, Drago F, et al. Red flags in primary mitochondrial diseases: what should we recognize? Int J Mol Sci. 2023;24(23):16746. doi:10.3390/ijms242316746
- Nicolau S, Milone M, Liewluck T. Guidelines for genetic testing of muscle and neuromuscular junction disorders. Muscle Nerve. 2021;64(3):255–269. doi:10.1002/mus.27337