One Gene Mutation Links Three Mysterious, Debilitating Diseases

iStock
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."

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Turn Your LEGO Bricks Into a Drone With the Flybrix Drone Kit

Flyxbrix/FatBrain
Flyxbrix/FatBrain

Now more than ever, it’s important to have a good hobby. Of course, a lot of people—maybe even you—have been obsessed with learning TikTok dances and baking sourdough bread for the last few months, but those hobbies can wear out their welcome pretty fast. So if you or someone you love is looking for something that’s a little more intellectually stimulating, you need to check out the Flybrix LEGO drone kit from Fat Brain Toys.

What is a Flybrix LEGO Drone Kit?

The Flybrix drone kit lets you build your own drones out of LEGO bricks and fly them around your house using your smartphone as a remote control (via Bluetooth). The kit itself comes with absolutely everything you need to start flying almost immediately, including a bag of 56-plus LEGO bricks, a LEGO figure pilot, eight quick-connect motors, eight propellers, a propeller wrench, a pre-programmed Flybrix flight board PCB, a USB data cord, a LiPo battery, and a USB LiPo battery charger. All you’ll have to do is download the Flybrix Configuration Software, the Bluetooth Flight Control App, and access online instructions and tutorials.

Experiment with your own designs.

The Flybrix LEGO drone kit is specifically designed to promote exploration and experimentation. All the components are tough and can totally withstand a few crash landings, so you can build and rebuild your own drones until you come up with the perfect design. Then you can do it all again. Try different motor arrangements, add your own LEGO bricks, experiment with different shapes—this kit is a wannabe engineer’s dream.

For the more advanced STEM learners out there, Flybrix lets you experiment with coding and block-based coding. It uses an arduino-based hackable circuit board, and the Flybrix app has advanced features that let you try your hand at software design.

Who is the Flybrix LEGO Drone Kit for?

Flybrix is a really fun way to introduce a number of core STEM concepts, which makes it ideal for kids—and technically, that’s who it was designed for. But because engineering and coding can get a little complicated, the recommended age for independent experimentation is 13 and up. However, kids younger than 13 can certainly work on Flybrix drones with the help of their parents. In fact, it actually makes a fantastic family hobby.

Ready to start building your own LEGO drones? Click here to order your Flybrix kit today for $198.

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How to Brew Your Own Fluorescent Beer at Home

The Odin
The Odin

If you're one of the many people who made their own sourdough starter in quarantine, you already know yeast is a living thing. That means its biological makeup can be tweaked using genetic engineering. As Gizmodo reports, that's exactly what a former NASA biologist has done to create his new fluorescent yeast kits.

A few years ago, Josiah Zayner left his job as a synthetic biologist for NASA to found The Odin, a company that lets anyone experiment with genetic science at home. His recently launched yeast kit accomplishes this in an eye-catching way. Thanks to a fluorescent protein from jellyfish, yeast that's been genetically modified with the kit glows green under a black or blue light.

Despite looking like a prop from a sci-fi film, the yeast is still yeast. That means it can be used in home-brewing projects if you want to take the science experiment a step further. According to Eater, yeast made with the kit ferments and fluoresces when added to honey and water. If you brew a batch of beer with the right amount of yeast, the final product will emit an otherworldly glow when viewed under a blacklight. The kit hasn't been FDA approved, but the company states the materials are nontoxic and nonallergenic, and beer made with it will still taste like beer.

You can purchase a fluorescent yeast kit from The Odin's online shop for $169. If you're looking for more ways to experiment with genetic technology at home, the company also sells kits that let you play with frog and bacteria DNA.

[h/t Gizmodo]