Mitochondrial myopathy presenting as fibromyalgia
A 41-year-old Caucasian woman presented to a Rheumatology clinic with the complaints of progressive exercise intolerance, fatigue, diffuse, myalgias, arthralgias and difficulty sleeping. The pain primarily involved her entire back and arms, and she reported multiple tender points all over her body. She had been diagnosed with fibromyalgia, and was treated with different medicals without any relief.
The most likely diagnosis of this presentation is
- Ankylosing Spondylitis
- Joint fractures
Fibromyalgia is characterized by chronic widespread pain and fatigue associated with pain lasting for longer than 3 months on both sides of the body, involving the upper and lower halves and presence of at least 11 out of 18 specific tender points over the body1. Several pathogenic mechanisms for fibromyalgia have been postulated with each passing year and historically, disordered sleep 2, circadian rhythm abnormalities 3, and hormonal imbalance 4 have been looked upon as potential causes, but the importance of these factors is unclear. Other explanations include genetic abnormalities, psychiatric disorders, and environmental stressors 5. Thus, treating fibromyalgia has always been a challenge for most clinicians. Earlier tricyclic antidepressants have been the most commonly used medications. Other medication groups used to treat fibromyalgia include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, opioid analgesics, sedatives, hypnotics and anti-inflammatories, but only a small group of patients respond, and most people do not have long-term benefit 6.
Her past medical history included hypothyroidism, cervical disc disease, hypertension and Raynaud's disease. The family history included breast carcinoma and hypertension to her mother, and lymphoma to her father. She has been taking lisinopril 5 mg daily and levothyroxine 25 μg daily. Other medications previously used included pregabalin, amitriptyline and gabapentin.
Examination and Laboratory Investigations
Her physical examination results were normal except for mild tenderness to palpation along her upper and lower back, and shoulders. The laboratory results showed creatine kinase (CK) = 325 U/L (normal range 0 to 150 U/L), normal comprehensive metabolic panel (CMP) and complete blood count (CBC), liver function tests and thyroid functions tests; a normal resting lactic acid = 1.6 mmol/L, and an elevated post-six-minute-walk lactic acid = 5 mmol/L (normal result < 2 mmol/L). Her ammonia levels were normal at rest and after 6 minute walk (14 μmol/L and 38 μmol/L respectively; normal 0 to 40 μmol/L). A muscle biopsy revealed several abnormalities including decreased levels of citric acid synthase (49% of normal), cytochrome c oxidase (53% of normal), succinate dehydrogenase (72% of normal), and nicotinamide adenine dinucleotide (NADH) dehydrogenase (73% of normal), thereby demonstrating a defect in the mitochondrial respiratory chain. Genome sequencing revealed multiple POLG1 polymorphisms (C-T polymorphism at 2254, and G-T polymorphism at 3708) and several mitochondrial genome polymorphisms (1438 A-G, 3992 C-T, 14365 C-T, 14582 A-G, and 4042 A-G).
The patient was started on a compound of Co-Q10 200 mg, creatine 1000 mg, carnitine 200 mg and folic acid 1 mg to be taken four times a day which showed significant improvement in her symptoms over a course of several months.
Mitochondrial myopathies are characterized by the most common inherited metabolic diseases 7. Similar to fibromyalgia, patients may present with muscle weakness, pain, fatigue and exercise intolerance that progressively worsens over time. Several steps are involved in Adenosine-5'-triphosphate (ATP) generation in the mitochondria, and defects in any part of the cycle may impair energy production leading to symptoms 8. These abnormalities in generation and utilization of ATP can be assessed by specific tests, which as in our patient pointed towards problems in energy metabolism 9.Genetic testing with sequencing of the mitochondrial genome and chromosomal genes affecting mitochondrial function may also be pursued. Mutations in POLG1 and several mitochondrial genome polymorphisms were noted.
The patient was started on a regimen of coenzyme Q10 (Co-Q10; ubiquinone), creatine, carnitine, folic acid and α-lipoic acid that transport electrons between complex I and complex III of the mitochondrial respiratory chain and has been shown to improve mitochondrial function. Moreover, Carnitine enhances transport of fatty acids into the mitochondria. Folic acid is a cofactor for several mitochondrial enzymes, while α-lipoic acid is a strong antioxidant 10. Although this treatment regimen was started several years after symptom onset, within the first few months our patient showed tremendous improvement. Her complaints dissipated gradually but showed sustained resolution of all symptoms.
The case depicts the possible role of mitochondrial disease in the pathogenesis of fibromyalgia, whereby not only is underlying defect identified at the molecular and genomic level, but with appropriate therapy, significant symptomatic improvement is also noted. Furthermore, the exact role of mitochondrial myopathy in the development of fibromyalgia needs better understanding of the disease to ensure adequate and effective patient care. The patients with fibromyalgia should be evaluated for sleep disorders, endocrine disorders such as hypothyroidism and metabolic disorders before a diagnosis of primary fibromyalgia is given.
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