One Gene Mutation Links Three Mysterious, Debilitating Diseases

iStock
iStock

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.

The Best Place to Park at the Mall, According to Science

Diy13/iStock via Getty Images Plus
Diy13/iStock via Getty Images Plus

It’s Black Friday, and you are entering the battlefield: a mall parking lot. You’re determined to nail that doorbuster deal, and quantities are limited. The field is already full of other combatants. You must find the perfect parking spot.

Do you grab the first one you see, or drive as close to the mall as you can and hover? Or, do you choose a tactic that lies somewhere between?

Parking at the mall has long frustrated drivers and taxed the minds of traffic engineers—but after working on the problem for three years, physicists Sidney Redner of the Santa Fe Institute and Paul Krapivsky of Boston University have gotten closer to a winning strategy. “There are lots of studies of parking lots, but it’s just that they’re so complicated, you don’t get any insight into what’s actually happening,” Redner tells Mental Floss.

Redner and Krapivsky, whose work employs statistical physics to make sense of large systems, simplified the messy dynamics of a parking lot by modeling it with a one-dimensional grid of cells, each representing a parking space. They tested three simple, yet realistic, parking strategies using basic probability theory. Their model tested the following strategies to see which one resulted in least time spent walking and driving in the parking lot:

Meek Strategy: Meek drivers park in the first open space they see, however distant it is from the mall. As a result, they often spend the most time walking to and from the mall.

Prudent Strategy: Prudent drivers look for the first open spot but then keep driving toward the mall. They continue to drive until they see a parked car and then park in the best open spot between that first open spot and that first parked car. There may be a block of open spaces between the first open space and the first parked car. From that block of open spaces, they choose the one closest to the mall.

Optimistic Strategy: Optimistic drivers drive as close to the mall as possible and look for a parking space close to the entrance. If they see one, they grab it. If there are none, they backtrack and choose the first open space they see. Optimistic drivers probably spend the most time driving and the least time walking. In the worst-case scenario, they end up parking back where a meek driver would have parked.

Naturally cautious drivers are more likely to default to the meek mode, while aggressive drivers often use the optimistic strategy, well, aggressively. And most drivers have tried something like the prudent method.

So, which is your best bet in a crowded mall parking lot this holiday season?

In the experiments, the prudent strategy fared best, followed closely by the optimistic strategy. The meek strategy finished a distant third (“It’s hard to comprehend just how bad it is,” says Krapivsky, a self-described meek driver).

And even better: The more crowded the lot, the better the prudent strategy works, he adds.

One clear takeaway from the study is that meek drivers may want to ramp up their parking skills before going to the mall. “You don't want to park on the very outskirts of the lot, like a mile away from the stores. You want to go to the first place there’s an open spot and park somewhere in that first open area,” Redner says. They published their findings in the Journal of Statistical Mechanics [PDF].

The researchers say this is the best of the strategies they tested, but it has its limitations. It does not take into consideration competition among a sea of drivers all looking for parking spaces at the same time, and it doesn’t include (perhaps optimistically) the psychological aspects of operating a vehicle. “We are not rational when we are driving,” Krapivsky tells Mental Floss.

The researchers’ one-dimensional grid model also assumed that there would be one car at a time entering the lot through one entrance, unlike messier lots in the real world, where many cars enter from a multitude of entrances.

The optimal parking strategy, one that would best all others every time, has yet to be found. In their research, though, Redner and Krapivsky are homing in on one that integrates the more complicated aspects of parking.

For now, science says prudence is a virtue in the parking lot. And while the meek might inherit the Earth, they certainly won’t find the best parking space at the mall.

'Lost Species' of Tiny, Rabbit-Sized Deer Photographed in Vietnam for the First Time in 30 Years

Global Wildlife Conservation
Global Wildlife Conservation

The silver-backed chevrotain, also called the Vietnamese mouse-deer, is elusive. It's so elusive that scientists had feared it was extinct after none had been photographed for decades. But as The Washington Post reports, the first images taken of the mammal in nearly 30 years prove that the species is still alive in the woods of Vietnam.

No larger than small dogs, chevrotains are the tiniest ungulates, or hoofed animals, on Earth. They have vampire-like fangs and skinny legs that support their bodies. Silver-backed chevrotains are characterized by the silver sheen of their tawny coat.

The tiny population native to Vietnam has been devastated by poachers in recent decades. That, and the animal's natural shyness, make it incredibly difficult to study. Before this most recent sighting, the last time scientists had recorded one was in 1990.

Global Wildlife Conservation, the Southern Institute of Ecology, and the Leibniz Institute for Zoo and Wildlife Research teamed up in hopes of documenting the lost species. Researchers interviewed residents and government forest rangers in the Vietnamese city of Nha Trang about the silver-backed chevrotain, looking for tips on where to find one. Residents said that while populations had been hit hard by hunting, the animals were still around.

Based on this local ecological knowledge, scientists set up three camera traps in the Vietnamese woods. In just five months, they captured 275 photographs of the little mouse-deer. They then installed 29 additional cameras and snapped 1881 new images in that same length of time.

“For so long this species has seemingly only existed as part of our imagination," Global Wildlife Conservation associate conservation scientist An Nguyen said in a statement. "Discovering that it is, indeed, still out there, is the first step in ensuring we don’t lose it again, and we’re moving quickly now to figure out how best to protect it.”

Now that a silver-backed chevrotain population has been located, researchers plan to conduct the first-ever comprehensive survey of the species. Once the data is collected, it will be used to build a plan for the species' survival.

[h/t The Washington Post]

SECTIONS

arrow
LIVE SMARTER