One Gene Mutation Links Three Mysterious, Debilitating Diseases


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."

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10 Facts You Should Know About Mosquitoes

tskstock/iStock via Getty Images
tskstock/iStock via Getty Images

Between the itching and the welts and the fears of mosquito-borne viruses, it's easy to forget that mosquitoes are a wonder of evolution, and that maybe they don't get a fair shake from us. Of more than 3000 known species, only 80 actually bite people, and at least one eats other mosquitoes for us. They grow from egg to adult in just five days, begin mating within minutes of hatching, and possess, by way of their stinging mouthparts, some of the coolest appendages in the animal kingdom.

1. Mosquitoes are excellent flyers in bad weather.

The average raindrop is 50 times heavier than the average mosquito, yet they buzz around in the rain with no problems. If a Boeing 747 got whacked with a similarly scaled-up raindrop, there would be 2375 tons of water coming down on it, and things probably wouldn’t turn out as well as they do for the mosquito. How do the insects do it?

A common urban legend said that the bugs were nimble enough to dodge the drops. A few years ago, a team of engineers from the Georgia Institute of Technology watched real mosquitoes and Styrofoam dummy mosquitoes with a high-speed camera during a rainy flight to see if that’s what was really happening. They found that the bugs don’t fly fast enough to dodge the drops, but their slowness is what keeps them from getting knocked out of the sky. A mosquito’s low mass even at slow speed doesn’t provide enough of a target for a raindrop to splash on collision. Instead, the drop just deforms, and doesn’t transfer enough momentum to the mosquito to disrupt its flight.

2. Texas is the mosquito capital of America.

Of the 3000 species of mosquitoes around the world, at least 150 are found in the United States, and 85 of those call Texas home. When people say everything's bigger in Texas, you can also include the biodiversity of the state's biting, disease-carrying insects.

3. Some mosquitoes are truly dangerous to humans ...

The female mosquito, which is the one that stings and sucks blood, is an incredible transmitter of disease and, because of that, the deadliest animal in the world. Each year, the malaria parasites they transmit kill 2 million to 3 million people and infect another 200 million or more. They also spread pathogens that cause yellow fever, dengue fever, Rift Valley fever, Chikungunya and West Nile disease.

4. ... and some mosquitoes are harmless.

Not every species of mosquito sucks blood from people, and among those that do, not every one transmits disease. The blood suckers don’t even need to bite you for every meal. Males live entirely on nectar and other plant fluids, and the females’ diet is primarily plant-based, too. Most of the time, they only go after people when they’re ready to reproduce, because blood contains lipids, proteins, and other nutrients needed for the production of eggs.

5. MosquitoEs actually help the environment.

When you’re rubbing calamine lotion all over yourself, mosquitoes might not seem to serve any purpose but to annoy you, but many species play important ecological roles. The mosquitoes Aedes impiger and Aedes nigripes, which gather in thick clouds in Arctic Russia and Canada, are an important food source for migrating birds. Farther south, birds, insects, spiders, salamanders, lizards, frogs, and fish also eat different mosquito species regularly. Plants need them, too, and some, like the blunt-leaved orchid and endangered monkeyface orchid, rely on mosquitoes as their primary pollinator.

Some mosquito species are also excellent at mosquito control. Species of the genus Toxorhynchites feed on the larvae and immature stages of other mosquitoes and will sometimes even cannibalize members of their own species.

6. Mosquitoes are amazing hunters (as if we needed to tell you that).

Mosquitoes are adept at picking up on the chemicals given off by their human hosts. They can detect the carbon dioxide in our breath, the 1-octen-3-ol in our breath and sweat, and other organic substances we produce with the 70-plus types of odor and chemical receptors in their antennae. These receptors can pick up traces of chemicals from hundreds of feet away, and once the mosquito closes in, it tracks its meal chemically and also visually—and they’re fond of people wearing dark colors.

7. Mosquitoes can be picky.

If it seems like you’re always covered head to toe by bites while people who were sitting right next to you only have one or two, it’s not just paranoia; the skeeters actually are out to get you. Some people happen to give off more of the odors and compounds that mosquitoes find simply irresistible, while others emit less of those and more of the compounds that make them unattractive to mosquitoes—either by acting as repellents or by masking the compounds that mosquitoes would find attractive.

8. A female mosquito's mouth is primed for sucking blood.

A mosquito doesn’t simply sink its proboscis into your skin and start sucking. What you see sticking out of a mosquito’s face is the labium, which sheaths the mouthparts that really do all the work. The labium bends back when a mosquito bites, allowing these other parts to pass through its tip and do their thing. The sharp, pointed mandibles and maxillae, which both come in pairs, are used to pierce the skin, and the hollow hypopharynx and the labrum are used to deliver saliva and draw blood, respectively.

9. Mosquito saliva prevents blood clotting.

The saliva that gets pumped out from the hypopharynx during a bite is necessary to get around our blood’s tendency to clot. It contains a grab bag of chemicals that suppress vascular constriction, blood clotting and platelet aggregation, keeping our blood from clogging up the mosquitoes' labrum and ruining their meal.

10. Mosquitoes can explode.

Blood pressure makes a mosquito's meal easier by helping to fill its stomach faster, but urban legend says it can also lead to their doom. Story goes, you can flex a muscle close to the bite site or stretch your skin taut so the mosquito can’t pull out its proboscis and your blood pressure will fill the bug until it bursts. The consensus among entomologists seems to be that this is bunk, but there is a more complicated way of blowing the bugs up. To make a blood bomb, you’ve got to sever the mosquito’s ventral nerve cord, which transmits information about satiety. When it's cut, the cord can’t tell the mosquito’s brain that its stomach is full, so it’ll keep feeding until it reaches critical mass. At least one researcher found that mosquitoes clueless about how full they were would keep sucking even after their guts had exploded, sending showers of blood spilling out of their blown-out back end.

Get The Details On All 21 Successful Moon Landings With This Interactive Map

Astronaut Eugene A. Cernan mans a Lunar Roving Vehicle during the Apollo 17 mission.
Astronaut Eugene A. Cernan mans a Lunar Roving Vehicle during the Apollo 17 mission.
NASA, Wikimedia Commons // Public Domain

In light of Apollo 11’s 50th anniversary this week, the world has focused on those historic first few steps on the Moon and everything that led up to them. But how much do you know about the 20 subsequent Moon landings? To fill you in, created an interactive map of the Moon with the who, what, where, when, and how of each successful lunar mission.

The map is color-coded: red for Russian Luna missions, green for China’s Chang'e 3 and Chang'e 4, and blue for the U.S.’s Apollo (marked with stars) and Surveyor missions (simple rings). You can click on each icon to expand a paragraph with a short summary of the mission and its notable accomplishments.

After Russia’s unmanned Luna 9 became the first craft to touch down on the Moon in 1966, 18 other triumphant landings followed in just a decade. The 20th didn’t happen until 37 years later, when China achieved its first landing with Chang'e 3 in 2013. The most recent occurred this past January, when China’s Chang'e 4 became the first spacecraft to land on the far side of the Moon. Chang'e 4 and its rover, Yutu 2, are still exploring the Moon as you read this, and China hopes to launch its follow-up mission, Chang'e 5, as early as this year.

Six Apollo missions landed humans on the Moon, and there haven’t been any actual astronauts on its surface since. But the 15 robotic landings have contributed to our lunar knowledge in a safer, more cost-efficient way. If you look at the map, you can see that most of the spacecrafts have landed near the Moon’s equator on the near side, where the terrain is mostly basaltic plains—the far side contains craters and even mountains. With more Chang'e missions to come from China, and NASA’s Artemis missions in the works, may soon have to create a 360° version of its map.