One Gene Mutation Links Three Mysterious, Debilitating Diseases

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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.

Could Gigantic Coconut Crabs Have Played a Part in Amelia Earhart’s Mysterious Disappearance? At Least One Scientist Thinks So

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Getty Images

Amelia Earhart's disappearance during her attempt to fly around the world has captivated historians and conspiracy theorists for more than 80 years. One organization is now suggesting that her fate may have been sealed by giant crabs.

The International Group for Historic Aircraft Recovery (TIGHAR) believes that Amelia Earhart and navigator Fred Noonan may have landed their plane on Nikumaroro Island when they couldn't find their target, Howland Island, and that Nikumaroro's endemic crustaceans may have played a part in the ensuing mystery.

According to National Geographic, there are several clues supporting TIGHAR's theory. The large reef that hugs Nikumaroro’s coast makes it conducive to emergency aircraft landings. In 1940—just three years after Earhart’s disappearance—British colonists found 13 human bones beneath a ren tree on the island and shipped them to Fiji, where they were lost. The colony's administrator, Gerald Gallagher, sent a telegram back to England positing that it was Earhart’s skeleton. Then, in 2001, researchers uncovered U.S.-made artifacts around the ren tree including a jackknife, a woman’s compact, a zipper, and glass jars. The plot thickened even further in 2017, when four forensic bone-sniffing dogs all indicated that a human had indeed died at the site, though excavators failed to dig up any more evidence.

If those 13 bones beneath the ren tree did belong to the unfortunate castaway, where are the rest of her remains? Tom King, TIGHAR’s former chief archaeologist, thinks that coconut crabs can answer that question.

Nikumaroro is home to thousands of the colossal creatures, which can grow to a terrifying 3 feet across and weigh 9 pounds. They’re sometimes called robber crabs because of their penchant for absconding with objects that smell like food, and they’ll eat practically anything—coconuts, fruit, birds, rodents, other crabs, their own discarded body parts, and carrion.

It’s not unreasonable, then, to think that coconut crabs may have feasted on Earhart’s corpse and then taken her bones home with them. In one experiment to test the theory, TIGHAR researchers deposited a pig carcass on the island and filmed the aftermath. With the help of small strawberry hermit crabs, coconut crabs stripped the pig down to the bone in two weeks. After a year, some of the bones had been dragged 60 feet from the carcass’s original location, and some were never recovered at all.

King believes Earhart’s missing 193 bones could be hidden in the burrows of various coconut crabs. As in the pig experiment, crabs may have scattered some of Earhart’s bones dozens of feet away, but maybe not all of them—after all, the forensic dogs smelled bones near the ren tree that haven’t yet been located. Right now, TIGHAR is working with the Canine Forensics Foundation to further explore the area.

While we wait for more answers, dive into these other theories about Earhart’s disappearance.

[h/t National Geographic]

10 Juicy Facts About Leeches

Ian Cook
Ian Cook

Leeches get a bad rap, but they’re actually pretty cool once you get to know them—and we're finding out more about them, even today. Recently, a team led by Anna Phillips, curator of parasitic worms at the Smithsonian National Museum of Natural History, discovered a new species of medicinal leech (pictured above) in a Maryland swamp. We asked parasite expert and curator at the American Museum of Natural History Mark E. Siddall to share some surprising facts about the worms we love to hate. 

1. Not all leeches suck blood.

Hematophagous, or blood-feeding, species are only one type of leech. “The vast majority of species are [hematophagous],” Siddall tells Mental Floss, “but it depends on the environment. In North America, there are probably more freshwater leeches that don’t feed on blood than there are blood-feeders.” And even among the hematophagous species, there are not too many who are after you. “Very few of them are interested in feeding on human blood,” Siddall says. “Certainly they’ll do it, if they’re given the opportunity, but they’re not what they’re spending most of their time feeding on.” 

2. Leeches are everywhere.

Japanese leech on a log
Pieria, Wikimedia Commons // Public Domain

“Every continent on the planet has leeches, with the exception of Antarctica,” Siddall says. “And even then there are marine leeches in Antarctic waters.” Humans have co-existed with leeches for so long, according to Siddall, that just about every language has a word for leech. 

3. Leeches have made a comeback in medicine.

Bloodletting for bloodletting’s sake has fallen out of favor with Western physicians, but that doesn’t mean medicinal leeches are enjoying a cushy retirement. Today, surgeons keep them on hand in the operating room and use them as mini-vacuums to clean up blood. “That is a perfectly sensible use of leeches,” Siddall says. Other uses, though, are less sensible: “The more naturopathic application of leeches in order to get rid of bad blood or to cure, I don’t know, whatever happens to ail you, is complete hooey,” he says. How on Earth would leeches take away bad blood and leave good blood? It’s silly.” 

4. Novelist Amy Tan has her own species of leeches.

Land-based leeches made an appearance in Tan’s 2005 book Saving Fish from Drowning, a fact that instantly put the author in leech researchers’ good graces. “There are not a lot of novels out there with terrestrial leeches in them,” Siddall says. So when he and his colleagues identified a new species of tiny terrestrial leeches, they gave the leech Tan’s name. The author loved it. “I am thrilled to be immortalized as Chtonobdella tanae,” Tan said in a press statement. “I am now planning my trip to Queensland, Australia, where I hope to take leisurely walks through the jungle, accompanied by a dozen or so of my namesake feeding on my ankles.”

5. Leeches can get pretty big.

The giant Amazon leech (Haementeria ghilianii) can grow up to 18 inches and live up to 20 years. And yes, this one’s a blood-feeder. Like all hematophagous species, H. ghilianii sticks its proboscis (which can be up to 6 inches long) into a host, drinks its fill, and falls off. Scientists thought the species was extinct until a zoologist found two specimens in the 1970s, one of whom he named Grandma Moses. We are not making this up.

6. Leeches make good bait.

Many walleye anglers swear by leeches. “A leech on any presentation moves more than other types of live bait," pro fisher Jerry Hein told Fishing League Worldwide. "I grew up fishing them, and I think they're the most effective live bait around no matter where you go." There’s an entire leech industry to provide fishers with their bait. One year, weather conditions kept the leeches from showing up in their typical habitats, which prevented their collection and sale. Speaking to CBS news, one tackle shop owner called the absence of leeches “the worst nightmare in the bait industry.”

7. Leech scientists use themselves as bait.

Siddall and his colleagues collect and study wild leeches. That means hours of trekking through leech territory, looking for specimens. “Whether we’re wandering in water or traipsing through a bamboo forest,” Siddall says, “we are relying on the fact that leeches are attracted to us.” Do the leeches feed on them? “Oh my god, yes. We try to get them before they feed on us … but sometimes, obviously, you can’t help it.”

8. Leech sex is mesmerizing.

Like many worms, leeches are all hermaphroditic. The specifics of mating vary by species, but most twine themselves together and trade sperm packets. (The two leeches in the video above are both named Norbert.)

9. Some leech species make surprisingly caring parents. 

“There’s a whole family of leeches that, when they lay their eggs, will cover them with their own bodies,” Siddall says. “They’ll lay the eggs, cover them with their bodies, and fan the eggs to prevent fungus or bacteria from getting on them, and then when the eggs hatch, they will attach to the parent. They’re not feeding on the parent, just hanging on, and then when the parent leech goes to its next blood meal it’s carrying its offspring to its next blood meal. That’s pretty profound parental care, especially for invertebrates.”

10. You might be the next to discover a new leech species. 

Despite living side-by-side with leeches for thousands of years, we’ve still got a lot to learn about them. Scientists are aware of about 700 different species, but they know there are many more out there. “I’ll tell you what I wish for,” Siddall says. “If you ever get fed on by a leech, rather than tearing off and burning it and throwing it in the trash, maybe observe it and see if you can see any color patterns. Understand that there’s a real possibility that it could be a new species. So watch them, let them finish. They’re not gonna take much blood. And who knows? It could be scientifically useful.”

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