Family History And Twin Studies
A 2001 study in the UK showed “there were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects.” Three twin studies showed that the correlations for prolonged and chronic fatigue were significantly higher in monozygotic than dizygotic twins for each definition of chronic fatigue syndrome.
What’s New On This Topic
Hypermobility Spectrum Disorders
The 2017 International Classification of the Ehlers-Danlos syndromes replaced prior terms for symptomatic joint hypermobility with hypermobile Ehlers-Danlos syndrome and introduced the term hypermobility spectrum disorder for patients not meeting hypermobile Ehlers-Danlos syndrome diagnostic criteria.
A 2013 U.K. population survey found that 3.4% of adults endorsed hypermobility and chronic widespread pain using validated instruments.
Generalized joint hypermobility is more common than hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders because patients with generalized joint hypermobility may be asymptomatic. When assessed in student population samples using the 2017 criteria, 4% to 11% of children three to 19 years of age had generalized joint hypermobility.
Home Remedies And Lifestyle Changes
Making some lifestyle changes may help reduce your symptoms.
Limiting or eliminating your caffeine intake can help you sleep better and ease your insomnia. You should limit or avoid nicotine and alcohol too.
Try to avoid napping during the day if its hurting your ability to sleep at night.
Create a sleep routine. Go to bed at the same time every night and aim to wake up around the same time every day.
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Evidence That Cfs Risk Is Inherited
Various observations are consistent with genetic factors contributing to CFS risk for some individuals. Individuals with a CFS diagnosis have a significant excess relatedness over the wider population for both close and distant relatives . Of three studies that have estimated narrow-sense heritability using large cohorts, two reported non-zero h2-values that provide evidence for heritability of risk for CFS and, presumably, ME/CFS. An analysis of US health insurance claimed a high narrow-sense heritability of CFS , whereas an analysis of the UK Biobank individuals self-reporting a CFS diagnosis reported a less striking heritability . The third, a large twin-based study of CFS-like cases, produced an inconclusive result, with the 95% confidence interval of h2 including zero .
The Idometabolic Trap Hypothesis For The Etiology Of Me/cfs
A new hypothesis, the indolamine-2,3-dioxygenase metabolic trap, was developed and formulated as a mathematical model. The historical occurrence of ME/CFS outbreaks is a singular feature of the disease and implies that any predisposing genetic mutation must be common. A database search for common damaging mutations in human enzymes produces 208 hits, including IDO2 with four such mutations. Non-functional IDO2, combined with well-established substrate inhibition of IDO1 and kinetic asymmetry of the large neutral amino acid transporter, LAT1, yielded a mathematical model of tryptophan metabolism that displays both physiological and pathological steady-states. Escape from the pathological one requires an exogenous perturbation. This model also identifies a critical point in cytosolic tryptophan abundance beyond which descent into the pathological steady-state is inevitable.
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Chronic Fatigue Syndrome Testing
In this blog, we will look at Chronic Fatigue Syndrome testing. You will learn:
- What Chronic Fatigue Syndrome is
- What testing is currently available
- How Functional Medicine can help in the case of Chronic Fatigue Syndrome
Do you suffer from severe fatigue, headaches or muscle or joint pain? Do you have Chronic Fatigue Syndrome and do you know how to address it? Then this blog is for you. Please read on for the details!
** Please note: If you want the longer, more detailed version of this article, then please click here **
What is Chronic Fatigue Syndrome?
Do Identified Differentially Methylated Dna Fragments And Differentially Methylated Individual Cytosines Relate To Me/cfs Pathophysiology
To determine whether the genomic elements associated with the DMFs and individual DMCs were identifying systemic changes relevant to ME/CFS pathophysiology, a functional enrichment analysis was performed through STRING.org v.11.0 . No significant enriched functional pathways were identified based on the differentially methylated promoter-associated genes through either the DMAP or MethylKit analysis.
Functional analysis was performed on the 31 genes associated with DMFs identified in the DMAP analysis and the 91 genes associated with the DMC analysis. Both STRING analyses were performed with the FDR P value cut-off of< 0.05. The enrichment analysis on the gene bodies associated with hyper- and hypo-methylated fragments identified in the DMAP analysis revealed a total of 22 functional pathways, 21 associated with hypo-methylated gene bodies and 1 associated with hyper-methylated gene bodies . From the 31 genes in the analysis, the enriched functional pathways associated with hypo-methylation were identified by various combinations of the following five genes: RYR1,GNAS,GNG7,GABRB3 and APBA3, and the single hyper-methylation-associated functional pathway was identified with two hyper-methylated genes: LCK and CIITA.
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Differential Methylation Within Gene Bodies
A significant proportion of the DMFs determined with DMAP were located in intron and exon regions . The DMAP fragment analysis identified 31 different genes within 31 fragments that had a total of 190 CpGs within them. The gene GNG7 was associated with the fragment that had the most statistically significant differentially methylated CpGs. GNG7 is a guanine nucleotide-binding protein with a large range of functions including the regulation of adenylyl cyclase in the brain. Information concerning the length of the associated fragment, number of CpGs within the fragment, and patient, control and differential methylation percentages is shown in Table . Significance scores are shown as P values and a corresponding F value.
Table 5 Top hypo-methylated and top hyper-methylated methylated fragment-associated gene bodies Table 6 Top hypo-methylated and hyper-methylated individual cytosines associated with gene bodies
Tables and list the differentially methylated genes linked to promoter regions identified, and Tables and the differentially methylated gene bodies with the two analysis platforms.
Me/cfs Community Breaking New Ground
Have ME/CFS become the first disease to uncover its own genetic roots.
When you dont get the big bucks, you have to find other ways to get the work done. Kudos to Dr. Klimas and her team for finding an innovative new way to get research done. This is the first crowd-sourcing effort the team knows of thats attempting to understand the genetic roots of a disease.
Its a great opportunity to make the NIH and other institutions sit up and get who we really are. Were not malingerers. Were not complainers. Were not just mad. Were smart, effective people who are so committed to the end of this illness that were taking matters into our hands. How many disease communities can say that?
Lets blow up their conceptions of ME/CFS and make ME/CFS the first disease community to uncover its own genetic roots. Maybe that will get them to move.
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Chronic Fatigue Syndrome: Diagnosis And Treatment
JOSEPH R. YANCEY, MD, Fort Belvoir Community Hospital, Fort Belvoir, Virginia
SARAH M. THOMAS, MD, Fairchild Air Force Base, Washington
Am Fam Physician. 2012 Oct 15 86:741-746.
Patient information: See related handout on chronic fatigue syndrome, written by the authors of this article.
Chronic fatigue syndrome is a widespread problem. It is estimated that more than 2 million Americans have CFS, many of whom have not been diagnosed.1 Women are twice as likely as men to have CFS,1 and it is more common in persons older than 40 years.1,2 There is not an established racial or educational predilection.1,2 CFS is often mentally and emotionally debilitating, and persons with this diagnosis are twice as likely to be unemployed as persons with fatigue who do not meet formal criteria for CFS.3 In 2002, the estimated annual cost of lost productivity was $9.1 billion dollars in the United States.4 In addition to economic hardships, persons with CFS are more likely to report subjective functional impairment than those with chronic fatigue.3
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Persons with chronic fatigue should have an evaluation, including history, physical examination, and initial laboratory testing .
SORT: KEY RECOMMENDATIONS FOR PRACTICE
Persons with chronic fatigue should have an evaluation, including history, physical examination, and initial laboratory testing .
Blood Test Might Diagnose Chronic Fatigue Syndrome
TUESDAY, April 30, 2019 — Chronic fatigue syndrome is such a mysterious illness that it took years to be recognized as a legitimate ailment, and doctors still struggle to accurately diagnose it.
Now, an experimental blood test has successfully spotted the syndrome, also known as CFS, in a finding that hopefully provides new insights into the inscrutable illness.
The test tracks changes in the electrical pattern of a person’s cells, and it accurately flagged all CFS patients in a small group of 40 people, researchers report.
“When we stress the cells, we can easily differentiate them based on the signal they are showing,” said lead author Rahim Esfandyarpour. “It’s a huge difference.”
Esfandyarpour worked on the test with a team while at Stanford University in California. He’s now an assistant professor of electrical engineering and computer science at the University of California, Irvine.
Currently, doctors must diagnose CFS based on the symptoms a patient has developed. There’s no lab test that can provide a definitive diagnosis.
“There is no biomarker or diagnostic tool,” Esfandyarpour said. “It’s all based on the symptoms.”
Sometimes people are even told it’s all in their imagination. As many as 2.5 million Americans suffer from CFS, and 9 of 10 have not been diagnosed, according to estimates from the U.S. Centers for Disease Control and Prevention.
So they created a way to track the metabolism of cells by observing their electrical activity.
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Genes Associated With Me/cfs
Researchers have identified dozens of genes that may be involved in ME/CFS. Studies have found changes in genes dealing with:
- Structure of the blood-brain barrier, what’s essentially a gatekeeper that keeps potentially harmful things from crossing from the bloodstream and into the brain
- The brain’s ability to learn and make new connections
- Immune-system activation not related to infection
- Regulation of the immune system
- Metabolic function, including sugar and fat processing
- Hormone activity
- Receptors of glutamate, a brain chemical known as a neurotransmitter
- Sensitivity to glucocorticoids, natural steroid hormones
- Stress-response system regulation
- Enzymes that affect DNA expression
- Functioning of T cells, a type of immune cell
One study found more than 100 changes to genes related to T cells alone. Some immune-system changes may even be an underlying mechanism of ME/CFS.
Genetic Predisposition For Immune System Hormone And Metabolic Dysfunction In Myalgic Encephalomyelitis/chronic Fatigue Syndrome: A Pilot Study
- 1Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States
- 2Department of Psychology and Neuroscience, Nova Southeastern University, Fort Lauderdale, FL, United States
- 3Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States
- 4Veterans Affairs Medical Center, Miami, FL, United States
- 5Department of Computer Science, Nova Southeastern University, Fort Lauderdale, FL, United States
Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome is a multifactorial illness of unknown etiology with considerable social and economic impact. To investigate a putative genetic predisposition to ME/CFS we conducted genome-wide single-nucleotide polymorphism analysis to identify possible variants.
Methods: 383 ME/CFS participants underwent DNA testing using the commercial company 23andMe. The deidentified genetic data was then filtered to include only non-synonymous and nonsense SNPs from exons and microRNAs, and SNPs close to splice sites. The frequencies of each SNP were calculated within our cohort and compared to frequencies from the Kaviar reference database. Functional annotation of pathway sets containing SNP genes with high frequency in ME/CFS was performed using over-representation analysis via ConsensusPathDB. Furthermore, these SNPs were also scored using the Combined Annotation Dependent Depletion algorithm to gauge their deleteriousness.
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Diagnosis Of Chronic Fatigue Syndrome
Laboratory tests to exclude other causes of symptoms
At least one of the following manifestations is also required:
Feeling of light-headedness or dizziness when standing up that is relieved by lying down
The frequency and severity of the symptoms should be assessed by a doctor. If people do not have these symptoms at least half of the time with moderate, substantial, or severe intensity, doctors reconsider the diagnosis of chronic fatigue syndrome .
Criteria for diagnosis are important mainly because they help doctors communicate clearly with each other when they study a problem. However, when treating a specific individual, doctors focus more on that person’s symptoms rather than the criteria.
Symptoms Of Chronic Fatigue Syndrome
Most people who have chronic fatigue syndrome are successful and function at a high level until the disorder begins, usually abruptly, often following a stressful event. The main symptom is fatigue that usually lasts at least 6 months and is severe enough to interfere with daily activities. Severe fatigue is present even on awakening and persists throughout the day. The fatigue often worsens with physical exertion or during periods of psychologic stress. However, physical evidence of muscle weakness or of joint or nerve abnormalities is absent. Extreme fatigue may begin during or after recovery from an illness that resembles a viral infection, with a fever, runny nose, and tender or painful lymph nodes. However, in many people, fatigue begins without any such preceding illness.
Other symptoms that may occur are difficulty concentrating and sleeping, sore throat, headache, joint pains, muscle pains, and abdominal pain. Depression is common, particularly when symptoms are severe or worsening. Symptoms often overlap with those of fibromyalgia Fibromyalgia Fibromyalgia is characterized by poor sleep, fatigue, mental cloudiness, and widespread aching and stiffness in soft tissues, including muscles, tendons, and ligaments. Poor sleep, stress, strains… read more , a possibly related disorder.
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Differential Methylation Within Promoter Regions Of Genes
Promoter regions were defined as being 1500 bp upstream and 500 bp downstream from the Transcription Start Site . Of the identified differentially methylated fragments , 16% were found within these defined promoter regions , and half were hypo-methylated and half hyper-methylated in ME/CFS patients compared to controls. Eleven different promoter regions were associated with twelve DMFs. The LOC339166 associated promoter region contained two adjacent statistically significant hypo-methylated fragments. The genes linked to promoter regions associated with the DMFs that show the most variation between the patients and controls are shown in Table , with values for both ME/CFS patients and healthy controls along with the P and F test values.
Table 3 Genes linked to promoter regions associated with the top DMFs
The MethylKit analysis identified a larger number of promoter-associated genes with 45 DMCs falling within 22 promoter regions. Of these individual cytosines, 69% were hypo-methylated in ME/CFS patients compared to controls. There were two methylated promoter-associated genes that overlapped between the DMAP and MethylKit analyses, LOC339166 and NUDT14. The region associated with LOC339166 encompasses the cluster described previously within chromosome 17, and identifies regulatory interactions for XAF1 and ZNF594. NUDT14 is important for the elimination of toxic metabolites as well as the regulation of nucleotide substrates, cofactors and signalling molecules.
How Is Cfs Diagnosed
CFS is a very challenging condition to diagnose.
According to the Institute of Medicine, as of 2015, CFS occurs in about 836,000 to 2.5 million Americans. Its estimated, however, that 84 to 91 percent have yet to receive a diagnosis.
There are no medical tests to screen for CFS. Its symptoms are similar to many other conditions. Many people with CFS dont look sick, so doctors may not recognize that they indeed have a health condition.
In order to receive a CFS diagnosis, your doctor will rule out other potential causes and review your medical history with you.
Theyll confirm that you at least have the core symptoms previously mentioned. Theyll also ask about the duration and severity of your unexplained fatigue.
Ruling out other potential causes of your fatigue is a key part of the diagnosis process. Some conditions with symptoms that resemble those of CFS include:
- severe obesity
- sleep disorders
Because of the similarities between symptoms of CFS and many other conditions, its important to not self-diagnose. Talk to your doctor about your symptoms. They can work with you to get relief.
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Biomarker For Chronic Fatigue Syndrome Identified
Stanford scientists devised a blood-based test that accurately identified people with chronic fatigue syndrome, a new study reports.
Ron Davis is the senior author of a paper that describes a blood test that may be able to identify chronic fatigue syndrome.Steve Fisch
People suffering from a debilitating and often discounted disease known as chronic fatigue syndrome may soon have something theyve been seeking for decades: scientific proof of their ailment.
Researchers at the Stanford University School of Medicine have created a blood test that can flag the disease, which currently lacks a standard, reliable diagnostic test.
Too often, this disease is categorized as imaginary, said Ron Davis, PhD, professor of biochemistry and of genetics. When individuals with chronic fatigue syndrome seek help from a doctor, they may undergo a series of tests that check liver, kidney and heart function, as well as blood and immune cell counts, Davis said. All these different tests would normally guide the doctor toward one illness or another, but for chronic fatigue syndrome patients, the results all come back normal, he said.
A paper describing the research findings was published online April 29 in the Proceedings of the National Academy of Sciences. Davis is the senior author. Esfandyarpour, who is now on the faculty of the University of California-Irvine, is the lead author.
General Exercise Tips For People With Chronic Fatigue Syndrome
Be guided by your doctor or specialist, but general suggestions include:
- Experiment to find the type of exercise that works best for you. Choose from a range of gentle activities such as stretching, yoga, tai chi, walking and light weight training.
- Keep an activity diary so you have a long-term picture of your performance levels and factors that might impact on your symptoms.
- Stop the physical activity well before you feel any symptom flare. Pacing yourself is very important.
- Remember that the amount of exercise you can do will change from one day to the next.
- Listen to your body if you dont feel up to exercising on a particular day, dont.
- Find out as much as you can about your ME/CFS. Make sure you consult with health professionals who fully understand ME/CFS as a ‘real’ biomedical condition.
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