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.

This Live Stream Lets You Eavesdrop on Endangered Killer Whales' Conversations

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iStock.com/Serega

Southern resident killer whales, which are usually found off the coasts of Washington, Oregon, and British Columbia, are an endangered species. If you're lucky, though, you might be able to hear a pod of the killer whales chattering away from the comfort of your own home. A website spotted by The Kansas City Star lets you live stream the calls of killer whales from your phone or laptop. Dubbed Orcasound, it uses hydrophones (underwater microphones) to pick up oceanic sounds from two areas off the coast of Washington.

On the website, listeners can choose between the two locations. One is the Orcasound Lab in Haro Strait, which is situated off the coast of Washington's San Juan Islands—the "summertime habitat" of this specific ecotype of whale, according to the website. The other location is Bush Point at the entrance to Puget Sound, where the whales pass through about once a month in search of salmon. However, that hydrophone is currently being repaired.

So what do orcas sound like? They're loud, and they do a whole lot of whistling, whining, and clicking. You can hear a snippet of what that sounds like in a four-minute podcast uploaded to the Orcasound site.

There’s no guarantee you’ll hear an orca, though. "Mostly you'll hear ships," the website notes, but there's also a chance you'll hear humpbacks in the fall and male harbor seals in the summer.

The live stream isn't just for educational purposes. It also serves as a citizen science project to help researchers continue their studies of southern resident killer whales, which are in danger of starvation as Chinook salmon, their main food source, die off.

The makers of Orcasound are urging listeners to email ihearsomething@orcasound.net anytime they hear killer whales or "other interesting sounds." They can also log their observations in a shared Google spreadsheet. Eventually, developers of the site hope to roll out a button that listeners can click when they hear a whale, to make the process easier for people to get involved.

[h/t The Kansas City Star]

How to Cook a Turkey for Thanksgiving, According to the Experts

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iStock.com/mphillips007

In a letter written to his daughter Sally in 1784, two years after the bald eagle was chosen as the country’s national emblem, Ben Franklin referred to the species as a “bird of bad moral character” that steals fish from weaker birds. A turkey, he argued, was a “much more respectable bird.”

But many Americans have a difficult time cooking turkey. Despite their fine moral fiber, turkeys have a reputation for being among the trickiest of birds to prepare. They're big and bulky, and cooking turkey to a safe temperature can easily dry out the meat. Techniques like brining and spatchcocking—essentially snapping the turkey’s spine in order to lay it flat—are best left to advanced chefs. So how can holiday hosts cook turkey to everyone’s satisfaction?

GET TO KNOW YOUR THANKSGIVING TURKEY

A turkey is placed into an oven
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It helps to understand what kind of fowl you’re dealing with. “The average Thanksgiving turkey is 12 or 14 pounds,” says Guy Crosby, Ph.D., an adjunct associate professor of nutrition at the Harvard School of Public Health. “That’s opposed to a 3- or 4-pound chicken. And dark meat tends to need a higher temperature to cook than white meat, which runs the risk of drying out the breast when you’re trying to get the rest of it cooked. People also want a nice, crisp brown skin. Balancing all of that with safety is a big challenge.”

Undercooking a turkey can be problematic, particularly if you’d prefer not to serve up a Petri dish of Salmonella to guests. The bacteria that causes food poisoning and all its unpleasant symptoms is commonly found in poultry and has even led to a recent 35-state outbreak of illness due to contaminated raw turkey products that were apparently mishandled by consumers. The good news? Cooking turkey to an internal temperature of 165°F will kill any germs lurking inside.

Still, you want to be careful in how you handle your raw materials. According to Sue Smith, co-director of the Butterball Turkey-Talk Line, you should avoid washing the turkey. “We don’t recommend it because there’s no reason,” Smith tells Mental Floss. “You don’t want [contaminated] water to splatter around the countertops.”

BRINE A TURKEY UNDER ITS SKIN

If you bought your turkey frozen, let it thaw breast-side up for four days in your refrigerator. (A good rule of thumb is one day for every four pounds of weight.) Place the bird in a pan and put it on the bottom shelf so no juices leak on to other shelves or into food.

Once it’s thawed, you can consider an additional step, and one that might make for a juicier bird. Rather than brine the entire turkey—which allows it to soak up saltwater to retain more moisture during cooking—you can opt to moisten the meat with a 1:1 salt and sugar mixture under the skin.

“Turkeys are so darn big that brining it is not something you can do conveniently in a fridge,” Crosby tells Mental Floss. “If you want to add salt to a turkey, the general recommendation is to salt it under the skin.” Crosby advises to use the salt and sugar blend anywhere meat is prone to drying out, like the breast. Let it rest in the fridge for 24 hours, uncovered. (That’s one day in addition to thawing. But check to make sure your turkey didn’t already come pre-brined.)

This accomplishes a few things. By adding salt to the meat, you’re going to let the meat retain more moisture than it would normally. (Cooking effectively squeezes water from muscle tissue, wringing the bird of its natural moisture.) By leaving it uncovered in the fridge, you’re letting the skin get a little dry. That, Crosby says, can encourage the Maillard reaction, a chemical response to heat in excess of 300 degrees that transforms amino acids and sugar, resulting in a tasty brown skin.

Once your bird is ready for roasting, Smith advises you to place the bird on a flat, shallow pan with a rack that raises it 2 or 3 inches. “The rack lets airflow get around the bottom,” she says. If you don’t have a flat rack, you can use carrots, celery, or even rolled tin foil to give the turkey a little boost off the pan.

COOK TURKEY TO A SAFE TEMPERATURE

Sliced turkey is served on a plate
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A 12- to 14-pound turkey will need to roast for roughly 3 hours at 350°F in order to cook thoroughly. But you’ll want to be sure by using a food thermometer. Both Smith and Crosby caution against trusting the disposable pop-up thermometers that come pre-inserted in some turkeys. Invest in a good oven-safe meat thermometer and plunge it right into the deepest space between the drumstick and thigh and get it to a safe 175 to 180 degrees. (The USDA's Food Safety and Inspection Service recommends heating it to no less than 165 degrees.) “By that point, the breast will be over 180 degrees,” Crosby says. If you’ve stuffed the turkey—and roughly half of people do, according to Butterball research—make sure it’s cooked to a temperature of at least 165 degrees.

Once your bird is done, let it sit out for 35 to 45 minutes. The turkey will retain enough heat that it won’t get cold (don't cover it with tin foil, because the crispy skin will get soggy). Instead, a cooling-off period allows the muscle fibers to reabsorb juices and the salt and sugar to bring out more of the flavor.

REHEAT LEFTOVER TURKEY SLOWLY

When it’s time to put the leftovers away, be sure to keep slicing. Individual portions will cool down more quickly than if you shoved the entire bird into the fridge. Eat them within two or three days. If you want to keep it from drying out during reheating, Crosby suggests putting the meat into a covered baking dish with some vegetables, potatoes, or gravy and using the oven on low heat or a saucepan on the stovetop. “You’ll retain more moisture the slower you reheat it,” he says.

Roasting isn’t the only approach, as some of your friends or family members may attest. In addition to the brutal triumph of spatchcocking, some people opt to deep-fry turkeys, grill them, or slice them up into pieces prior to cooking. There’s no wrong way, but roasting will give you the most predictable results.

“Roasting is Butterball’s preferred method,” Smith says. “It consistently turns out a tender, juicy turkey.” Or, as Ben Franklin would say, a much more respectable bird.

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