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.

15 Gripping Facts About Galileo

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Albert Einstein once said that the work of Galileo Galilei “marks the real beginning of physics.” And astronomy, too: Galileo was the first to aim a telescope at the night sky, and his discoveries changed our picture of the cosmos. Here are 15 things that you might not know about the father of modern science, who was born February 15, 1564.

1. There's a reason why Galileo Galilei's first name echoes his last name.

You may have noticed that Galileo Galilei’s given name is a virtual carbon-copy of his family name. In her book Galileo’s Daughter, Dava Sobel explains that in Galileo’s native Tuscany, it was customary to give the first-born son a Christian name based on the family name (in this case, Galilei). Over the years, the first name won out, and we’ve come to remember the scientist simply as “Galileo.”

2. Galileo Galilei probably never dropped anything off the leaning tower of Pisa. 

With its convenient “tilt,” the famous tower in Pisa, where Galileo spent the early part of his career, would have been the perfect place to test his theories of motion, and of falling bodies in particular. Did Galileo drop objects of different weights, to see which would strike the ground first? Unfortunately, we have only one written account of Galileo performing such an experiment, written many years later. Historians suspect that if Galileo taken part in such a grand spectacle, there would be more documentation. (However, physicist Steve Shore did perform the experiment at the tower in 2009; I videotaped it and put the results on YouTube.)

3. Galileo taught his students how to cast horoscopes.

It’s awkward to think of the father of modern science mucking about with astrology. But we should keep two things in mind: First, as historians remind us, it’s problematic to judge past events by today’s standards. We know that astrology is bunk, but in Galileo’s time, astrology was only just beginning to disentangle from astronomy. Besides, Galileo wasn’t rich: A professor who could teach astrological methods would be in greater demand than one who couldn’t.

4. Galileo didn't like being told what to do.

Maybe you already knew that, based on his eventual kerfuffle with the Roman Catholic Church. But even as a young professor at the University of Pisa, Galileo had a reputation for rocking the boat. The university’s rules demanded that he wear his formal robes at all times. He refused—he thought it was pretentious and considered the bulky gown a nuisance. So the university docked his pay.

5. Galileo Galilei didn't invent the telescope.

We’re not sure who did, although a Dutch spectacle-maker named Hans Lipperhey often gets the credit (he applied for a patent in the fall of 1608). Within a year, Galileo Galilei obtained one of these Dutch instruments and quickly improved the design. Soon, he had a telescope that could magnify 20 or even 30 times. As historian of science Owen Gingerich has put it, Galileo had managed “to turn a popular carnival toy into a scientific instrument.”

6. A king leaned on Galileo to name planets after him.

Galileo rose to fame in 1610 after discovering, among other things, that the planet Jupiter is accompanied by four little moons, never previously observed (and invisible without telescopic aid). Galileo dubbed them the “Medicean stars” after his patron, Cosimo II of the Medici family, who ruled over Tuscany. The news spread quickly; soon the king of France was asking Galileo if he might discover some more worlds and name them after him.

7. Galileo didn't have trouble with the church for the first two-thirds of his life.

In fact, the Vatican was keen on acquiring astronomical knowledge, because such data was vital for working out the dates of Easter and other holidays. In 1611, when Galileo visited Rome to show off his telescope to the Jesuit astronomers there, he was welcomed with open arms. The future Pope Urban VIII had one of Galileo’s essays read to him over dinner and even wrote a poem in praise of the scientist. It was only later, when a few disgruntled conservative professors began to speak out against Galileo, that things started to go downhill. It got even worse in 1616, when the Vatican officially denounced the heliocentric (sun-centered) system described by Copernicus, which all of Galileo’s observations seemed to support. And yet, the problem wasn’t Copernicanism. More vexing was the notion of a moving Earth, which seemed to contradict certain verses in the Bible.

8. Galileo probably could have earned a living as an artist.

We think of Galileo as a scientist, but his interests—and talents—straddled several disciplines. Galileo could draw and paint as well as many of his countrymen and was a master of perspective—a skill that no doubt helped him interpret the sights revealed by his telescope. His drawings of the Moon are particularly striking. As the art professor Samuel Edgerton has put it, Galileo’s work shows “the deft brushstrokes of a practiced watercolorist”; his images have “an attractive, soft, and luminescent quality.” Edgerton writes of Galileo’s “almost impressionistic technique” more than 250 years before Impressionism developed.

10. Galileo wrote about relativity long before Einstein.

He didn’t write about exactly the same sort of relativity that Einstein did. But Galileo understood very clearly that motion is relative—that is, that your perception of motion has to do with your own movement as well as that of the object you’re looking at. In fact, if you were locked inside a windowless cabin on a ship, you’d have no way of knowing if the ship was motionless, or moving at a steady speed. More than 250 years later, these ideas would be fodder for the mind of the young Einstein.

10. Galileo never married, but that doesn't mean he was alone.

Galileo was very close with a beautiful woman from Venice named Marina Gamba; together, they had two daughters and a son. And yet, they never married, nor even shared a home. Why not? As Dava Sobel notes, it was traditional for scholars in those days to remain single; perceived class difference may also have played a role.

11. You can listen to music composed by Galileo's dad.

Galileo’s father, Vincenzo, was a professional musician and music teacher. Several of his compositions have survived, and you can find modern recordings of them on CD (like this one). The young Galileo learned to play the lute by his father’s side; in time he became an accomplished musician in his own right. His music sense may have aided in his scientific work. With no precision clocks, Galileo was still able to time rolling and falling objects to within mere fractions of a second.

12. His discoveries may have influenced a scene in one of Shakespeare's late plays.

An amusing point of trivia is that Galileo and Shakespeare were born in the same year (1564). By the time Galileo aimed his telescope at the night sky, however, the English playwright was nearing the end of his career. But he wasn’t quite ready to put down the quill: His late play Cymbeline contains what may be an allusion to one of Galileo’s greatest discoveries—the four moons circling Jupiter. In the play’s final act, the god Jupiter descends from the heavens, and four ghosts dance around him in a circle. It could be a coincidence—or, as I suggest in my book The Science of Shakespeare, it could hint at the Bard's awareness of one of the great scientific discoveries of the time.

13. Galileo had some big-name visitors while under house arrest.

Charged with “vehement suspicion of heresy,” Galileo spent the final eight years of his life under house arrest in his villa outside of Florence. But he was able to keep writing and, apparently, to receive visitors, among them two famous Englishmen: the poet John Milton and the philosopher Thomas Hobbes.

14. Galileo's bones have not rested in peace.

When Galileo died in 1642, the Vatican refused to allow his remains to be buried alongside family members in Florence’s Santa Croce Basilica; instead, his bones were relegated to a side chapel. A century later, however, his reputation had improved, and his remains (minus a few fingers) were transferred to their present location, beneath a grand tomb in the basilica’s main chapel. Michelangelo is nearby.

15. Galileo might not have been thrilled with the Vatican's 1992 "apology."

In 1992, under Pope John Paul II, the Vatican issued an official statement admitting that it was wrong to have persecuted Galileo. But the statement seemed to place most of the blame on the clerks and theological advisers who worked on Galileo’s case—and not on Pope Urban VIII, who presided over the trial. Nor was the charge of heresy overturned.

Additional sources: The Discoveries and Opinions of Galileo; Galileo's Daughter; The Cambridge Companion to Galileo.

10 Things You Should Know About Asthma

iStock.com/Wojciech Kozielczyk
iStock.com/Wojciech Kozielczyk

To anyone with asthma, the feeling of an attack is unmistakable. Patients have compared an asthma attack's feeling of breathlessness, caused by inflammation in the lungs and airways, to being smothered by a pillow or having an elephant sit on their chest. Medical experts have already figured out some aspects of asthma, like how to diagnose and treat it, but other components, like what causes asthma and how to cure it, remain unclear. From the triggers people encounter at work to the connection to allergies, here are some facts about asthma symptoms and treatments you should know.

1. Asthma attacks are related to allergies.

The physical process that occurs when someone has a sneezing fit during pollen season is similar to what happens during an asthma attack. But while the former causes discomfort, the latter produces potentially life-threatening symptoms. When people with allergies are exposed to an allergen like pollen, they produce antibodies that bind to that allergen. This signals the body to release the chemicals that cause allergic symptoms. In most people, the symptoms are limited to the head, such as a runny nose or watery eyes, but in people with asthma, they're felt in the lungs. If the lungs are inflamed, the airways that carry air swell up and fill with mucus, constricting airflow and causing common asthma symptoms like coughing, wheezing, and shortness of breath. Such asthma attacks can be fatal when patients can’t get enough air to their lungs.

2. Asthma is the most prevalent chronic disease among children.

Asthma is common, affecting 25 million in the U.S. alone, and of those patients, about 7 million are children. Most people with the disease develop it during childhood. Asthma is the most prevalent chronic illness among kids, and each year, students miss 13.8 million school days because of it.

3. Asthma may be inherited.

Doctors aren’t entirely sure what causes asthma, but they know it sometimes runs in families. A 2010 study found that people with one parent with the condition were nearly twice as likely to have it themselves, and people with a parent and a grandparent with asthma were four times more likely to develop it. Because asthma is connected to allergies, a genetic disposition toward allergies, known as atopy, may explain some inherited asthma cases.

4. Asthma is surprisingly easy to diagnose.

One of the simplest ways to diagnose asthma is through a lung function test. If a patient is reporting asthma symptoms (coughing, chest tightness, a feeling of not getting enough air), their doctor may check the strength of their exhalations before and after having them use an inhaler. If their breathing improves with the medicine, they likely have asthma. An X-ray of the patient’s chest can also be used to reach an asthma diagnosis.

5. Kids who grow up around germs are less likely to have asthma.

A person’s environment early in life may also play a role in whether or not they develop asthma. People who grew up in rural areas, around animals, and in large families are less likely to have asthma than those who did not. One possible explanation is the hygiene hypothesis: According to this theory, kids who were exposed to germs and pathogens while their immune systems were developing are better equipped to deal with allergens, while kids who were sheltered from germs may be more likely to have an exaggerated (and in the case of asthma, potentially deadly) immune response to harmless substances. The hygiene hypothesis hasn’t been proven, however, and it’s definitely not an excuse to expose children to infections in an attempt to strengthen them against asthma attacks in the future.

6. Asthma triggers are everywhere.

To manage their symptoms, doctors tell asthma patients to limit exposure to their triggers when possible. Common asthma triggers include irritants and allergens like dust, tobacco smoke, car exhaust, mold, pet dander, and smoke from burning wood. Triggers that don’t come from the environment, like colds, sinus infections, acid reflux, and hyperventilation brought on by stress, can be even harder to avoid.

7. There's one asthma trigger patients shouldn't avoid.

Physical activity causes fast breathing, which can provoke asthma attacks in some people with the condition. There’s even a type of asthma called exercise-induced bronchoconstriction that specifically describes people who suffer from these kinds of attacks. But the risks of living a sedentary lifestyle outweigh those of exercising carefully, even with asthma. Instead of cutting out cardio altogether, doctors work with patients to come up with an exercise plan that’s safe for them. This might include warming up and using an inhaler before working out, practicing cool-down activities afterward, and wearing scarves or masks to limit exposure to irritants that may also trigger asthma symptoms.

8. There are two types of asthma treatments.

Long-term controllers and quick-relievers are the two types of medications used to treat asthma. Immediate medicines like short-acting beta agonists and anticholinergics relax muscles in the airways when flare-ups occur, and they’re typically administered directly to the lungs with an inhaler. Long-term medications help keep asthma symptoms under control over time are taken as often as once a day, regardless of whether symptoms are present. They include inhaled long-acting beta agonists and corticosteroids, biologic injections, and theophylline and leukotriene modifier pills and liquids. All of these medications suppress asthma symptoms by either relaxing muscles, reducing swelling, or preventing inflammation in the airways.

9. Asthma can be an occupational hazard.

Occupational asthma develops when a patient’s triggers come from their work environment. According to the National Institutes of Health, wood dust, grain dust, animal dander, fungi, and various chemicals are some of the most common asthma triggers that patients encounter in the workplace. Bakers, farmers, laboratory workers, millers, and woodworkers predisposed to asthma are all at higher risk.

10. There's no cure for asthma, but symptoms can lessen over time.

Though asthma is treatable, there’s no cure for the chronic illness. Some people, however, do appear to grow out of the condition after suffering from it as kids. It’s possible for asthma symptoms to become less severe and go into remission as patients get older, but once someone is diagnosed with asthma, the risk of an episode never goes away completely. Changes in hormone levels are a factor that could possibly bring asthma symptoms back in patients who haven’t experienced an attack in years.

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