List of rare and uncommon diseases: differential and mis – diagnosis in ME/CFS

There is/are no substantive data on the frequency at which ME/CFS is a misdiagnosis – that is where a patient with a serious illness is misdiagnosed as having ME/CFS.

Despite the lack of data a misdiagnosis of ME/CFS undoubtedly happens and while differential and exclusionary diagnoses should identify common diseases that might be confused with ME/CFS, there are many rare and uncommon diseases that are not routinely tested for. In the UK (population 67 million) 1 in 17 will be diagnosed with a ‘rare’ disease at some point in their life What is a rare disease ?

This thread is to list both rare and uncommon diseases that may need to be considered when ME/CFS is differentially diagnosed but which are not included in current testing regimes.

 

Empty Sella Syndrome

"Empty sella syndrome (ESS) is a disorder that involves the sella turcica, a bony structure at the base of the brain that surrounds and protects the pituitary gland. ESS is often discovered during imaging tests for pituitary disorders. An individual with ESS may have no symptoms or may have symptoms resulting from partial or complete loss of pituitary function including"

Link Between Empty Sella Syndrome, Fibromyalgia, and Chronic Fatigue Syndrome: The Role of Increased Cerebrospinal Fluid Pressure

Paper discussed here: https://www.s4me.info/threads/the-l...pressure-2023-hulens-et-al.31664/#post-457772

 

This topic is of interest to me. From memory, rare diseases found in apparent ME/CFS patients included a case of glycogen storage disease, multiple cases of muscle ion channel disorders, multiple cases of mitochondrial disorders, Parkinson's disease, a congenital structural cardiovascular disorder (not 100% clear), and some muscle diseases. Also a case of periodic fever syndrome (not sure which subtype).

The suspicion is that muscle diseases are overrepresented but it's difficult to say without knowing what would be expected. Perhaps diagnostics for muscular disorders are just better than for many other kinds of diseases, even if it can take much time before a diagnosis is made.

There also exists a genetic disorder which is said to resemble ME/CFS, although it's not clear if that similarity is with respect to Fukuda CFS or modern case definitions. It's corticosteroid binding globulin deficiency and it's extremely rare which is probably why it's never discussed on the forum.

There is probably also some misdiagnosis between MS, ME/CFS, and autoimmune disorders, and between ME/CFS and hormone disorders.

Some of these misdiagnoses could be due to the Fukuda criteria. It would be interesting to see if using PEM mandatory criteria reduces misdiagnosis rates.

 

Babesiosis is considered rare. It can mimic ME/CFS.

Ditto for B Miyamotoi, which is a relapsing fever and I believe is still considered rare.

I second channelopathies.

 

I am doubtful that there is justification for including Empty Sella Syndrome specifically. Low pituitary function of any cause might produce symptoms misdiagnosed as ME. (I doubt ESS would produce symptoms for other reasons.) The paper quoted suggesting that changes in CSF pressure may be relevant looks highly speculative. I think we need to be careful not to pick up on fringe theories that may make people seek advice that will be readily offered by fringe physicians without sound evidence.

 

Perhaps an alternative co-thread might be common diseases with inadequate diagnostics that could be misdiagnosed as ME/CFS.

 

I can appreciate this sentiment. But there may be rare or fringe cases that might not be considered as such if they are tested for - and found - more often. When my wife tested positive for her rare channelopathy gene she was only one of less than 100 in the entire world. Five years later and it's many times that amount because neurologists and geneticists have begun to look for it more often.

It is a conundrum, admittedly.

 

I was talking about fringe theories rather than 'fringe cases'. What I mean by a fringe theory is something that most people who look carefully would judge to be vague or incoherent speculation. Highlighting rare diseases makes sense. Highlighting academic babble doesn't.

 

Even after failing to find a genetic cause for my symptoms, I still believe there is something genetic to be found in my family. It's not normal for two people to have fatigue and poor tolerance of upright posture, along with various other issues, including one typical infection associated agravation of the illness lasting years. And a third person with daily syncope for years. And a fourth with fatigue and cognitive impairment. All with adolescent or young adult onset. One person recovered completely.

 

It could be a good idea for ME/CFS clinics to begin using genetic testing in selected families with multiple cases of ME/CFS or similar illnesses. The cost of testing is going down every year, the tools available are improving as well. If this is done, it should be only a matter of time until some discoveries are made about rare risk genes for ME/CFS, or about other kinds of illnesses that can kind of look like ME/CFS.

The DecodeME GWAS will not be able to find the rare variants, only the more common ones.

 

I recall that Sanofi either gave a grant to Crawley or is running a study with her at the University of Bristol on detecting Pompe disease in children diagnosed with ME/CFS. Sanofi’s incentive is financial as they sell a very expensive treatment for the disease.

There has been at least one case report of mitochondrial myopathy misdiagnosed as ME/CFS.

 

Perhaps your family has a combination of genes that all contribute a small mount, hence no "smoking gun."

 

I have several SNPs that were associated with orthostatic hypotension in this study: https://pubmed.ncbi.nlm.nih.gov/22504314/

From what I understand the effect of each of these SNPs is small. And OH related SNPs don't explain the whole range of symptoms.

 

Extract - "A thorough search of the PubMed and Web of Science databases and the reference lists of the included studies revealed that several clinical characteristics were more prevalent in primary ES, FM or CFS patients than in controls, including increased cerebrospinal fluid pressure, obesity, female sex, headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss), and bodily pain (radicular pain and small-fiber neuropathy)."


"increased cerebrospinal fluid pressure" - moderate increases in pressure cannot be measured directly - correct?

"headaches and migraine, fatigue, visual disturbances (visual acuity and eye motility abnormalities), vestibulocochlear disturbances (vertigo and neurosensorial hearing loss)" - I assume that the DecodeME/Biobanks study questionnaire will ask questions about headaches - correct? So if there was a significant group, with a moderate increases in "cerebrospinal fluid pressure", then that should be identifiable?

 

Comments above make me wonder if GWAS (DecodeME) could identify relevant genes i.e. if this is more common in people with MECFS?