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.

Not-So-Fancy Feast: Your Cat Probably Would Eat Your Rotting Corpse

Tycson1/iStock via Getty Images
Tycson1/iStock via Getty Images

Cat enthusiasts often cite the warmth and companionship offered by their pet as reasons why they’re so enamored with them. Despite these and other positive attributes, cat lovers are often confronted with the spurious claim that, while their beloved furry pal might adore them when they’re alive, it won’t hesitate to devour their corpse if they should drop dead.

Though that’s often dismissed as negative cat propaganda spread by dog people, it turns out that it’s probably true. Fluffy might indeed feast on your flesh if you happened to expire.

A horrifying new case study published in the Journal of Forensic Sciences offers the fresh evidence. The paper, first reported by The Washington Post, documents how two cats reacted in the presence of a corpse at Colorado Mesa University’s Forensic Investigation Research Station, or body farm, where the deceased are used to further forensic science for criminal investigations.

The study’s authors did not orchestrate a meeting between cat and corpse. The finding happened by accident: Student and lead author Sara Garcia was scanning surveillance footage of the grounds when she noticed a pair of cats trespassing. The cats, she found, were interested in the flesh of two corpses; they gnawed on human tissue while it was still in the early stages of decomposition, stopping only when the bodies began leaching fluids.

The cats, which were putting away one corpse each, didn’t appear to have a taste for variety, as they both returned to the same corpse virtually every night. The two seemed to prefer the shoulder and arm over other body parts.

This visual evidence joins a litany of reports over the years from medical examiners, who have observed the damage left by both cats and dogs who were trapped in homes with deceased owners and proceeded to eat them. It’s believed pets do this when no other food source is available, though in some cases, eating their human has occurred even with a full food bowl. It’s something to consider the next time your cat gives you an affectionate lick on the arm. Maybe it loves you. Or maybe it has something else in mind.

[h/t The Washington Post]

Wolf Puppies Play Fetch, Too, Study Finds

Christina Hansen Wheat
Christina Hansen Wheat

It took thousands of years of selective breeding for wolves to become the Golden Retrievers you see at dog parks today. Domesticated dogs are very different from their wild counterparts, but according to a new study, they may have a surprising trait in common. Researchers found that some wolf puppies are willing to play fetch with total strangers, suggesting that following human commands is intrinsic to canines.

For their study in the journal iScience, researchers from Stockholm University in Sweden set out to find how domestication affects behaviors in young wolves. They raised litters of wolf and dog pups separately from 10 days old and placed them in various scenarios.

When the scientists tested how the wolf puppies would respond to a game of fetch, they expected to be ignored. Chasing a ball and bringing it back requires understanding human commands and obeying them—abilities that were thought to only have emerged in dogs post-domestication.

The first two wolf groups met expectations by showing little interest in the toy, but something different happened with the third set. Three eight-week old pups went after the ball and brought it back when they were encouraged to do so. This was the case even when the person giving the commands was someone they had never met before.

Even though most of the puppies didn't play fetch, the fact that those who did belonged to the same litter indicates a "standing variation" for a retrieving trait in wolves. "When you talk about a specific trait in the context of standing variation, it means that there is variation for the expression of this trait within a given population," co-author Christina Hansen Wheat tells Mental Floss. "For our study it suggests that, while probably rare, standing variation in the expression of human-directed behavior in ancestral populations could have been an important target for early selective pressures exerted during dog domestication." In other words, ancient people seeking to domesticate wolves might have focused on some wolves' innate ability to follow human commands.

The first dogs were domesticated as far back as 33,000 years ago. Over millennia, humans have selected for traits like loyalty, friendliness, and playfulness to create the modern dog, but these new findings could mean that the dog's earliest canine ancestors were genetically predisposed toward some of these behaviors.

"All three litters were brought up under identical and standardized conditions across years," Hansen says of the pups in the study. "With this significant effort to control the environmental conditions, it is likely that the differences in behavior across litters to some extent have a genetic basis."

After raising the dog and wolf litters for three years and completing that part of their study, the researchers will continue to analyze their data to see if there are any other adorable (or weird) traits the two groups share.

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