One Gene Many Disorders: Genetic Finding Could Help Explain POTS, EDS, IBS, FM, ME/CFS and Others | Health Rising| Oct 20, 2016.

First, at least for me [Cort Johnson], there was chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM). Then I learned about irritable bowel syndrome (IBS), then POTS and in the last five years Ehler’s-Danlos (EDS) and Mast Cell Activation Syndrome (MCAS).

The more researchers looked the more they seemed to uncover a large group of syndromes which tended to flock together.

Anyone who has ME/CFS or FM now has to consider whether they also might have

dysautonomia,

IBS,

POTS,

MCAS and

a host of other disorders (interstitial cystitis, migraine, multiple chemical sensitivities, small fiber neuropathy).

Obviously, this suite of disorders is connected somehow, but the question – what is the tie that binds? – has remained.

Now the NIH of all groups – never really a friend to any of these – may have uncovered a link – that may explain them for some people.

Family Study

Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. (I’ve included the study itself below this article)

The researchers zeroed in on a set of families with these problems and studied them intensively.

First, increased levels of an immune factor called tryptase which is sometimes associated with mast cell activation showed up.

Despite the high tryptase levels they believed the disease they uncovered was more akin to connective tissue disorders such as Ehlers-Danlos Syndrome (EDS) than MCAS.

Mast cells have often been implicated in certain functional disorders; however,

our patients did not have evidence of clonal mast cell disease or evidence of mast cell activation ,

whereas

many did have connective tissue manifestations overlapping with those seen in EDS III.

Of the 96 people from 35 family’s studies, almost

50% met the criteria for IBS

65% met the criteria for chronic gastroesophageal reflux

28% had joint hypermobility

48% had arthritis

47% had headache, or body pain

a full quarter had congenital skeletal problems

46% had autonomic issues and

34% had POTS.

Other common issues included

flushing and pruritus (51%)

itching and sleep disruption (39%) and

exaggerated reactions to venom.

Extra Sequences Spell Trouble

Further testing found that individuals containing multiple copies of a tryptase encoding sequence were highly, highly likely (p<.000001) to have high tryptase levels.

Tryptase is the most common enzyme found in mast cells and is often used as a marker for mast cell activation.

Interestingly, none of the individuals had evidence of mast cell activation syndrome.

If tryptase was causing their symptoms, it was doing so in a different way than is ordinarily associated with MCAS. (MCAS is apparently called a syndrome for a reason.).

A retrospective analysis of people who’d had genomic analyses done for other disorders indicated that all the individuals with increased serum tryptase levels had multiple copies of the tryptase encoding sequence.

Next, the researchers turned to a healthy control group, and again found that all the individuals with increased tryptase levels had multiple copies of the tryptase encoding gene.

New Disease

It’s rare that genetic effects are so clear.

In fact, the genetic effects were so clear that the condition is now called hereditary-a tryptasemia. This disease is “exclusively caused” by increased copy numbers of the tryptase-producing sequence.

The study highlights, though, that it’s not necessary to understand a disease to find a treatment for it.

Knowing that elevated tryptase levels cause pain, connective tissue problems and orthostatic intolerance, even if we don’t know how, can allow researchers to develop anti-tryptase blockers that could conceivably stop these symptoms in their tracks.

Tryptase can be tested for, and in fact, around five percent of the population, or over 15 million people in the U.S. have high tryptase levels.

Most of them are probably asymptomatic but those who are ill could benefit greatly from this finding. It’s very rare to find such a clear genetic link and such a clear treatment pathway.

NIH Admits It Was Not “All in Their Heads” After All

The NIH itself noted that this study should give hope to people with complex multi-system disorders who, too often, have ended up being told their unusual symptoms must be “all in their head”.

It’s not often that a clear cause of an illness – let alone a spectrum of illnesses – may have been found. In fact, the NIH was so excited that it produced a video about the finding and sent out a press release

Plus, seeing NIAID crow over its genetic finding for a complex multi-symptom condition is a good thing.

One of the reasons NIAID abandoned ME/CFS was because it was a complex multi-symptom, multi-systemic condition.