Clinically proven mtDNA mutations are not common in those with chronic fatigue syndrome

Abstract

BackgroundChronic Fatigue Syndrome (CFS) is a prevalent debilitating condition that affects approximately 250,000 people in the UK. There is growing interest in the role of mitochondrial function and mitochondrial DNA (mtDNA) variation in CFS. It is now known that fatigue is common and often severe in patients with mitochondrial disease irrespective of their age, gender or mtDNA genotype. More recently, it has been suggested that some CFS patients harbour clinically proven mtDNA mutations.MethodsMtDNA sequencing of 93 CFS patients from the United Kingdom (UK) and South Africa (RSA) was performed using an Ion Torrent Personal Genome Machine. The sequence data was examined for any evidence of clinically proven mutations, currently; more than 200 clinically proven mtDNA mutations point mutations have been identified.ResultsWe report the complete mtDNA sequence of 93 CFS patients from the UK and RSA, without finding evidence of clinically proven mtDNA mutations. This finding demonstrates that clinically proven mtDNA mutations are not a common element in the aetiology of disease in CFS patients. That is patients having a clinically proven mtDNA mutation and subsequently being misdiagnosed with CFS are likely to be rare.ConclusionThe work supports the assertion that CFS should not be considered to fall within the spectrum of mtDNA disease. However, the current study cannot exclude a role for nuclear genes with a mitochondrial function, nor a role of mtDNA population variants in susceptibility to disease. This study highlights the need for more to be done to understand the pathophysiology of CFS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0387-6) contains supplementary material, which is available to authorized users.

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

“…Our laboratory previously reported no association between mitochondrial SNPs and ME/CFS, although some SNPs correlated with specific symptoms in patients (26). Others have also found no clinically relevant mitochondrial SNPs in patients with ME/CFS (27,28).…”

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome

“…However, due to a lack of definitive evidence across the CFS population others have suggested that such an association is not significant [ 23 , 27 , 28 ]. Two research groups have independently shown that clinically validated pathogenic mtDNA mutations are likely to be very rare in CFS cohorts [ 29 , 30 ]. One study did not find any clinically validated mtDNA mutations at significant heteroplasmy levels, while the other found only one, a LHON (Leber hereditary optic neuropathy) mutation.…”

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

“…The main ME/CFS symptoms, such as fatigue, exercise intolerance, and myalgia, are also shared by patients diagnosed with primary mitochondrial disorders (Filler et al, 2014;Gorman et al, 2015). However, unlike the mitochondrial dysfunction observed in mitochondrial disorders, which is known to be caused by mutations in either nuclear or mitochondrial DNA (mtDNA) (Tomas et al, 2017), these mutations in patients with ME/CFS are extremely rare (Billing-Ross et al, 2016;Schoeman et al, 2017). In addition, certain mitochondrial enzymes have been found to discriminate between mitochondrial disorders and ME/CFS.…”