One Gene Mutation Links Three Mysterious, Debilitating Diseases

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On a good day, my shoulders, knees, and hips will dislocate two to five times apiece. The slightest bump into a table or door will bloom new bruises on my arms and legs or tear a gash in the thin skin on my hands. My blood pressure will plummet each time I stand, making me feel woozy, nauseated, and weak. I’ll have trouble focusing and remembering words. I’ll run my errands from underneath an umbrella to prevent an allergic reaction to the Sun.

I have Ehlers-Danlos Syndrome (EDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS)—a trifecta of weird diseases. POTS, EDS, and MCAS are so obscure that many doctors have never even heard of them. But a 2016 study published in Nature Genetics might help change that: Researchers have found a genetic mutation that links all three conditions.

There are at least six types of EDS, all caused by defective connective tissue. I’ve got the most common form, Hypermobility Type (EDS-HT), also known as EDS-III. EDS-HT is considered the most “benign” form—that is, it’s generally not fatal—but the chronic pain, injuries, and other symptoms it causes can easily take over a person’s life.

POTS is a form of dysautonomia, or dysfunction of the autonomic nervous system (ANS). The ANS manages all the things your body does without thinking, from breathing and pumping blood to digesting food. My POTS is pretty mild; at the moment, the hardest parts are the fatigue and the cognitive issues caused by decreased blood flow to my brain. Other people are not so lucky and may need feeding tubes or constant bed rest.

MCAS, also called Mast Cell Activation Disease, is the newest and potentially the trickiest of the three. Mast cells are generally heroes in the body, helping keep the immune system alert and responsive. But some people have paranoid mast cells that can perceive just about anything (foods, medications, temperatures, deep breathing) as a threat. And when they go off, there’s no telling what will happen; researchers have implicated mast cell activation issues in dozens of symptoms and conditions, from anaphylactic shock to irritable bowel syndrome as well as dysautonomia and connective tissue problems.

People who have EDS-HT often also have POTS or MCAS or both, yet the relationships between the three remain murky. Some scientists think EDS causes POTS. Others think MCAS causes POTS and EDS. But we don’t really know, because there’s been barely any research on any of them. It’s hard to study conditions that look different in every patient (I've never met anyone else with one of these conditions who has a sunlight allergy) and have few, if any, quantifiable symptoms. Another reason for the lack of scientific interest? All three conditions are far more common in women, a trait long associated with meager research funding and minimal medical concern.

Consequently, there are no FDA-approved tests for these diseases, and there are certainly no cures. People with EDS-HT wear joint braces to reduce dislocations and are taught to manage their pain. People with POTS are prescribed beta blockers, high-sodium diets, and compression gear to keep up their blood pressure. People with MCAS are given antihistamines.

EDS-HT is typically passed from parent to child, and scientists have found genetic markers for other types of EDS, so it’s not unreasonable to think that it could be caused by mutated DNA.

Fortunately, the cost of DNA sequencing has continued to drop, and clusters of researchers around the world are beginning to take a look. The latest study, led by Joshua Milner at the National Institute of Allergy and Infectious Diseases, involved 96 people with EDS-HT and mast cell issues. POTS symptoms were common, especially gut problems like Irritable Bowel Syndrome.

The study participants had another thing in common: higher-than-normal levels of a protein called tryptase in their blood. Tryptase is part of the immune system’s reaction and has been linked to a handful of core EDS-HT and POTS symptoms, Milner says.

"Tryptase can contribute to pain sensitivity," he told me. "It can contribute to blood vessels doing funny things, and it can contribute to how your connective tissue, your bones and joints, are made."

Most people with mast cell issues actually have normal levels of tryptase, so the group Milner and his colleagues tested represented just a small subset of mast cell patients. But that subset did seem to have a unique genetic signature: an extra copy of a gene called TPSAB1. Under normal circumstances, TPSAB1 makes a form of tryptase called alpha-tryptase. People with a double dose of the gene are getting a double dose of the protein, too.

Armed with this clue, the researchers then went back through thousands of patient records for healthy people. When they looked at the DNA results of people with high tryptase levels, they found that all of them also had the TPSAB1 mutation. The scientists then interviewed a number of these supposedly hearty specimens and found that all of them were living with symptoms that sounded suspiciously similar to those of EDS-HT, POTS, and MCAS. They'd just never been diagnosed. (This is unsurprising—the average time to diagnosis for a person with EDS-HT is 10 years.)

In short, Milner and his team had discovered a genetic biomarker for Ehlers-Danlos Syndrome. Now, EDS-HT is a very variable condition, and the few experts that do exist suspect it's actually a bunch of different diseases called by the same name. Still, this finding represents one possible clinical test for what has been an un-testable illness.

Alpha-tryptase is a funny thing. About 30 percent of people don't make it at all, and they seem just fine without it, which means that a potential treatment pathway for the EDS-HT/MCAS/POTS hat trick could involve simply shutting down the alpha-tryptase factory.

It’s "interesting work," says Lawrence Afrin, a hematologist at the University of Minnesota. He told me the study represents "early progress toward further unraveling these illnesses." And Afrin should know: he's one of the leading MCAS experts in the country.

He agrees that alpha-tryptase could be a promising avenue for treatment. "But if I've learned anything about [MCAS]," he says, "it's that it's incredibly complex. Hopefully, with another 10,000 studies, we'll make 10,000 more bits of progress."

In the meantime, people with EDS, POTS, and MCAS have found other ways to cope. Communities of patients have popped up in cities across the globe and all over Twitter, Tumblr, and elsewhere on the web. These illnesses can be incredibly isolating and lonely—but, as I've learned, none of us are alone.

If you recognize yourself or your symptoms in this story, read up on the basics of EDS, MCAS, and POTS, and brace yourself for an uphill battle.

"Find a local physician who’s willing to learn," Afrin advises.

"And try to be patient," Milner says. "I know it's hard, but stick with it. We're all figuring this out together."

Know of something you think we should cover? Email us at tips@mentalfloss.com.

Feeling Stressed? Playing Tetris Could Help Relieve Your Anxiety

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iStock/Radachynskyi

When Nintendo released their handheld Game Boy system in the U.S. and Japan in 1989, the first game most users experimented with was Tetris. Bundled with the system, the clever puzzler—which prompts players to line up a descending array of tiles to create horizontal lines—was the video game equivalent of an addictive drug. Some players described seeing the shapes in their dreams. The game was in the hands of 35 million portable players; by 2010, it had sold 100 million smartphone downloads.

Now, there’s evidence that Tetris players may have a solution to anxiety in the palms of their hands. According to a paper published in the journal Emotion, Tetris has the capability to relieve stress and troubling thoughts by providing a form of distraction.

As part of a larger study about the benefits of distraction, researchers at the University of California, Riverside conducted an experiment on 309 college students who were told to expect some anxiety-provoking news: They were told someone would be offering an evaluation of their physical attractiveness. While they waited for their results, a third of the subjects played a slow-moving, beginner-level version of Tetris; another group played a high-speed variation; and a third played an adaptive version, which automatically adjusted the speed of the game based on the player’s abilities.

Tetris games that were too slow or too fast bored or frustrated players, respectively. But the game that provided a moderate challenge helped reduce the subjects’ perception of their stress levels. They reported a quarter-point higher level of positive emotions on a five-point scale and a half-point reduction of negative emotions. The students still worried about the results of the attractiveness evaluation, but they experienced fewer negative feelings about it.

The key, according to the study, is that the students were experiencing “flow,” a state of mind in which you’re so engrossed in an activity that you lose your sense of self-awareness. While Tetris may be one of the best ways to quickly fall into flow, anything that consumes your attention—playing music, drawing, cooking—is likely to work.

The next time you have to wait for potentially life-altering news, you may find that a Tetris session will help you cope.

[h/t NPR]

9 Fascinating Facts About the Vagus Nerve

The vagus nerve is so named because it “wanders” like a vagabond, sending out sensory fibers from your brainstem to your visceral organs. The vagus nerve, the longest of the cranial nerves, controls your inner nerve center—the parasympathetic nervous system. And it oversees a vast range of crucial functions, communicating motor and sensory impulses to every organ in your body. New research has revealed that it may also be the missing link to treating chronic inflammation, and the beginning of an exciting new field of treatment for serious, incurable diseases. Here are nine facts about this powerful nerve bundle.

1. THE VAGUS NERVE PREVENTS INFLAMMATION.

A certain amount of inflammation after injury or illness is normal. But an overabundance is linked to many diseases and conditions, from sepsis to the autoimmune condition rheumatoid arthritis. The vagus nerve operates a vast network of fibers stationed like spies around all your organs. When it gets a signal for incipient inflammation—the presence of cytokines or a substance called tumor necrosis factor (TNF)—it alerts the brain and draws out anti-inflammatory neurotransmitters that regulate the body’s immune response.

2. IT HELPS YOU MAKE MEMORIES.

A University of Virginia study in rats showed that stimulating their vagus nerves strengthened their memory. The action released the neurotransmitter norepinephrine into the amygdala, which consolidated memories. Related studies were done in humans, suggesting promising treatments for conditions like Alzheimer’s disease.

3. IT HELPS YOU BREATHE.

The neurotransmitter acetylcholine, elicited by the vagus nerve, tells your lungs to breathe. It’s one of the reasons that Botox—often used cosmetically—can be potentially dangerous, because it interrupts your acetylcholine production. You can, however, also stimulate your vagus nerve by doing abdominal breathing or holding your breath for four to eight counts.

4. IT'S INTIMATELY INVOLVED WITH YOUR HEART.

The vagus nerve is responsible for controlling the heart rate via electrical impulses to specialized muscle tissue—the heart’s natural pacemaker—in the right atrium, where acetylcholine release slows the pulse. By measuring the time between your individual heart beats, and then plotting this on a chart over time, doctors can determine your heart rate variability, or HRV. This data can offer clues about the resilience of your heart and vagus nerve.

5. IT INITIATES YOUR BODY'S RELAXATION RESPONSE.

When your ever-vigilant sympathetic nervous system revs up the fight or flight responses—pouring the stress hormone cortisol and adrenaline into your body—the vagus nerve tells your body to chill out by releasing acetylcholine. The vagus nerve’s tendrils extend to many organs, acting like fiber-optic cables that send instructions to release enzymes and proteins like prolactin, vasopressin, and oxytocin, which calm you down. People with a stronger vagus response may be more likely to recover more quickly after stress, injury, or illness.

6. IT TRANSLATES BETWEEN YOUR GUT AND YOUR BRAIN.

Your gut uses the vagus nerve like a walkie-talkie to tell your brain how you’re feeling via electric impulses called “action potentials". Your gut feelings are very real.

7. OVERSTIMULATION OF THE VAGUS NERVE IS THE MOST COMMON CAUSE OF FAINTING.

If you tremble or get queasy at the sight of blood or while getting a flu shot, you’re not weak. You’re experiencing “vagal syncope.” Your body, responding to stress, overstimulates the vagus nerve, causing your blood pressure and heart rate to drop. During extreme syncope, blood flow is restricted to your brain, and you lose consciousness. But most of the time you just have to sit or lie down for the symptoms to subside.

8. ELECTRICAL STIMULATION OF THE VAGUS NERVE REDUCES INFLAMMATION AND MAY INHIBIT IT ALTOGETHER.

Neurosurgeon Kevin Tracey was the first to show that stimulating the vagus nerve can significantly reduce inflammation. Results on rats were so successful, he reproduced the experiment in humans with stunning results. The creation of implants to stimulate the vagus nerve via electronic implants showed a drastic reduction, and even remission, in rheumatoid arthritis—which has no known cure and is often treated with the toxic drugs—hemorrhagic shock, and other equally serious inflammatory syndromes.

9. VAGUS NERVE STIMULATION HAS CREATED A NEW FIELD OF MEDICINE.

Spurred on by the success of vagal nerve stimulation to treat inflammation and epilepsy, a burgeoning field of medical study, known as bioelectronics, may be the future of medicine. Using implants that deliver electric impulses to various body parts, scientists and doctors hope to treat illness with fewer medications and fewer side effects.

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