Dysautonomia in Mitochondrial Disease and Myopathy
Dysautonomia, including POTS, is a recognized complication of mitochondrial disease, particularly in patients with mitochondrial myopathy, with approximately 38-44% of patients developing some form of autonomic dysfunction. 1
Prevalence and Association
Mitochondrial diseases represent a spectrum of disorders caused by defects in mitochondrial function. When examining the relationship between mitochondrial disease and dysautonomia:
- Mitochondrial myopathies often present with multi-system involvement, including autonomic dysfunction 2
- The 2017 ACC/AHA/HRS guidelines specifically mention Kearns-Sayre Syndrome, a mitochondrial myopathy, as associated with significant His-Purkinje disease that can cause syncope 3
- Cardiac autonomic neuropathy (CAN) is a common form of dysautonomia in mitochondrial disorders, with prevalence increasing with disease duration 3
POTS in Mitochondrial Disease
POTS specifically has been documented in patients with mitochondrial cytopathy:
- In a single-center study of patients with confirmed mitochondrial cytopathy, 4 out of 6 patients demonstrated a postural orthostatic tachycardia response during tilt-table testing 4
- These patients presented with classic POTS symptoms including fatigue, palpitations, near syncope, and syncope 4
- The most common symptoms reported by POTS patients include palpitations (100%), lightheadedness (96%), and headache (87%), though sleep disturbances, gastrointestinal complaints, and temperature sensitivity are also common 5
Myopathy and Dysautonomia Connection
The specific combination of myopathy and dysautonomia without other manifestations is less well-documented, but evidence suggests:
- Mitochondrial myopathies can present with isolated muscle involvement before developing other systemic manifestations 3
- In a case series of patients with POTS, one patient was found to have McArdle disease (a metabolic myopathy), suggesting myopathies can be associated with dysautonomia 6
- Cardiopulmonary exercise testing in patients with mitochondrial myopathy shows abnormal oxygen utilization patterns with exaggerated circulatory responses, which may contribute to autonomic dysfunction 3
Diagnostic Considerations
When evaluating patients with suspected mitochondrial myopathy and dysautonomia:
- Head-up tilt testing is valuable for confirming orthostatic intolerance in these patients 4
- Tests that return abnormal results in patients with dysautonomia include natural killer cell function tests, tilt table or NASA lean test, and tests looking for abnormal brain perfusion 3
- Cardiopulmonary exercise testing can help differentiate between cardiovascular limitations and primary mitochondrial dysfunction 3
- Muscle biopsy with histochemical staining remains essential for definitive diagnosis of metabolic myopathies 2
Clinical Implications
The co-occurrence of dysautonomia and mitochondrial disease has important clinical implications:
- Patients with mitochondrial disease should be screened for symptoms of orthostatic intolerance
- Treatment approaches should address both the underlying mitochondrial dysfunction and the autonomic manifestations
- Exercise intolerance is a key feature of both conditions, requiring specialized exercise protocols 7
- Pharmacotherapy for orthostatic symptoms has shown benefit in patients with mitochondrial cytopathy and POTS 4
Conclusion
Dysautonomia, including POTS, represents a significant but often underrecognized complication of mitochondrial disease. While the exact prevalence is not precisely documented in large epidemiological studies, case series and clinical guidelines acknowledge this association. The combination of myopathy with dysautonomia can occur either as part of a broader mitochondrial syndrome or, less commonly, as the predominant clinical manifestation. Clinicians should maintain a high index of suspicion for autonomic dysfunction when evaluating patients with mitochondrial myopathy, particularly those with unexplained fatigue, exercise intolerance, or orthostatic symptoms.