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."

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Amazon's Best Black Friday Deals: Tech, Video Games, Kitchen Appliances, Clothing, and More

Amazon
Amazon

This article contains affiliate links to products selected by our editors. Mental Floss may receive a commission for purchases made through these links.

Black Friday is finally here, and Amazon is offering great deals on kitchen appliances, tech, video games, and plenty more. We will keep updating this page as sales come in, but for now, here are the best Amazon Black Friday sales to check out.

Kitchen

Instant Pot/Amazon

- Instant Pot Duo Plus 9-in-115 Quart Electric Pressure Cooker; $90 (save $40)

- Keurig K-Cafe Special Edition; $190 (save $30)

- Ninja OS301 Foodi 10-in-1 Pressure Cooker and Air Fryer; $125 (save $75)

- Nespresso Vertuo Next Coffee and Espresso Machine by Breville; $120 (save $60)

- KitchenAid KSMSFTA Sifter with Scale Attachment; $95 (save $75)

- Keurig K-Mini Coffee Maker; $60 (save $20)

- Cuisinart Bread Maker; $80 (save $97)

- Anova Culinary Sous Vide Precision Cooker; $139 (save $60)

- Aicook Juicer Machine; $35 (save $15)

- JoyJolt Double Wall Insulated Espresso Mugs - Set of Two; $14 (save $10)

- Longzon Silicone Stretch Lids - Set of 14; $16 (save $11)

- HadinEEon Milk Frother; $37 (save $33)

Home Appliances

Roomba/Amazon

- iRobot Roomba 675 Robot Vacuum with Wi-Fi Connectivity; $179 (save $101)

- ASAKUKI 500ml Premium Essential Oil Diffuser; $22 (save $4)

- Facebook Portal Smart Video Calling 10 inch Touch Screen Display with Alexa; $129 (save $50)

- Bissell air320 Smart Air Purifier with HEPA and Carbon Filters; $280 (save $50)

- Oscillating Quiet Cooling Fan Tower; $59 (save $31)

- TaoTronics PTC 1500W Fast Quiet Heating Ceramic Tower; $55 (save $10)

- Vitamix 068051 FoodCycler 2 Liter Capacity; $300 (save $100)

- Ring Video Doorbell; $70 (save $30)

Video games

Sony

- Marvel's Spider-Man: Game of The Year Edition for PlayStation 4; $20 (save $20)

- The Legend of Zelda: Link's Awakening; $40 (save $20)

- Hyrule Warriors: Age of Calamity; $50 (save $10)

- Marvel's Avengers; $25 (save $33)

- The Last of Us Part II for PlayStation 4; $30 (save $30)

- LEGO Harry Potter: Collection; $15 (save $15)

- Ghost of Tsushima; $40 (save $20)

- BioShock: The Collection; $20 (save $30)

- The Sims 4; $24 (save $20)

- God of Warfor PlayStation 4; $10 (save $10)

- Days Gonefor PlayStation 4; $20 (save $6)

- Luigi's Mansion 3 for Nintendo Switch; $40 (save $20)

Computers and tablets

Microsoft/Amazon

- New Apple MacBook Pro 16 inches with 512 GB; $2149 (save $250)

- Microsoft Surface Laptop 3 with 13.5 inch Touch-Screen; $1200 (save $400)

- Lenovo ThinkPad T490 Laptop; $889 (save $111)

- Amazon Fire HD 10 Tablet (64GB); $120 (save $70)

- Amazon Fire HD 10 Kids Edition Tablet (32 GB); $130 (save $70)

- Apple iPad Mini (64 GB); $335 (save $64)

- Vankyo MatrixPad S2 Tablet; $120 (save $10)

Tech, gadgets, and TVs

Apple/Amazon

- Apple Watch Series 3 with GPS; $120 (save $79)

- Seneo Wireless Charger, 3 in 1 Wireless Charging Station; $16 (save $10)

- SAMSUNG 75-inch Class Crystal 4K Smart TV; $998 (save $200)

- Nixplay 2K Smart Digital Picture Frame 9.7 Inch Silver; $238 (save $92)

- All-New Amazon Echo Dot with Clock and Alexa (4th Gen); $39 (save $21)

- MACTREM LED Ring Light 6" with Tripod Stand; $16 (save $3)

- Amazon Fire TV Stick with Alexa Voice Remote; $28 (save $12)

- DR. J Professional HI-04 Mini Projector; $93 (save $37)

Headphones and speakers

Beats/Amazon

- Beats Solo3 Wireless On-Ear Headphones; $120 (Save $80)

- Apple AirPods Pro; $169 (save $50)

- Anker Soundcore Upgraded Bluetooth Speaker; $22 (save $8)

- Powerbeats Pro Wireless Earphones; $175 (save $75)

- JBL Boombox; $280 (save $120)

Movies and TV

HBO/Amazon

- Game of Thrones: The Complete Series; $115 (save $89)

- Jurassic World 5-Movie Set; $23 (save $37)

- Deadwood: The Complete Series; $42 (save $28)

- Back to the Future Trilogy; $15 (save $21)

Toys and Games

Amazon

- Awkward Family Photos Greatest Hits; $15 (save $10)

- Exploding Kittens Card Game; $10 (save $10)

- Cards Against Humanity: Hidden Gems Bundle; $14 (save $5)

- LOL Surprise OMG Remix Pop B.B. Fashion Doll; $29 (save $6)

- LEGO Ideas Ship in a Bottle 92177 Expert Building Kit; $56 (save $14)

Furniture

Casper/Amazon

- Casper Sleep Element Queen Mattress; $476 (save $119)

- ZINUS Alexis Deluxe Wood Platform Bed Frame; $135 (save $24)

- ROMOON Dresser Organizer with 5 Drawers; $59 (save $11) 

- AmazonBasics Room Darkening Blackout Window Curtains; $26 (save $5)

- Writing Desk by Caffoz; $119 (save $21)

- SPACE Seating Office Support Managers Chair; $112 (save $116)

- Rivet Globe Stick Table Lamp; $53 (save $17)

- Christopher Knight Home Merel Mid-Century Modern Club Chair; $188 (save $10)

- Walker Edison Furniture Industrial Rectangular Coffee Table; $121 (save $48)

Beauty

Haus/Amazon

- MySmile Teeth Whitening Kit with LED Light; $21 (save $12) 

- Cliganic USDA Organic Lip Balms Set of Six; $6 (save $4)

- HAUS LABORATORIES By Lady Gaga: LE RIOT LIP GLOSS; $7 (save $11)

- Native Deodorant for Men and Women Set of Three; $25 (save $11) 

- BAIMEI Rose Quartz Jade Roller & Gua Sha; $14 (save $3)

- Honest Beauty Clearing Night Serum with Pure Retinol and Salicylic Acid; $20 (save $8)

- WOW Apple Cider Vinegar Shampoo and Hair Conditioner Set; $30 (save $5) 

- La Roche-Posay Effaclar Purifying Foaming Gel Cleanser; $15 (save $5)

- wet n wild Bretman Rock Shadow Palette; $9 (save $6)

- EltaMD UV Daily Tinted Face Sunscreen Moisturizer with Hyaluronic Acid; $25 (save $6)

Clothes

Ganni/Amazon

- Ganni Women's Crispy Jacquard Dress; $200 (save $86) 

- The Drop Women's Maya Silky Slip Skirt; $36 (save $9)

- Steve Madden Women's Editor Boot; $80 (save $30)

- adidas Women's Roguera Cross Trainer; $40 (save $25)

- Line & Dot Women's Elizabeth Sweater; $74 (save $18)

- Levi's Men's Sherpa Trucker Jacket; $57 (save $41)

- Adidas Men's Essentials 3-Stripes Tapered Training Joggers Sweatpants; $28 (save $12)

- Timex Men's Weekender XL 43mm Watch; $32 (save $20)

- Ray-Ban Unisex-Adult Hexagonal Flat Lenses Sunglasses; $108 (save $46) 

- Reebok Men's Flashfilm Train Cross Trainer; $64 (save $16)

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How Much Is the Earth Worth?

The New York Public Library, Unsplash
The New York Public Library, Unsplash

Our home planet may be the most precious place we know, but it isn't priceless. The Earth's resources and the value it offers to humans add up to some unknown, tangible cost. The species may never have to worry about buying or selling the world, but thinking of it in terms of concrete numbers can help us better understand its value. Now, as Treehugger reports, one scientist has developed a special formula that allows us to do just that.

According to the calculations of Greg Laughlin, an assistant astronomy and astrophysics professor from the University of California, Santa Cruz, the Earth is worth roughly $5 quadrillion (or $5,000,000,000,000,000). He came up with that price after gauging the planet's mass, temperature, age, and other factors that directly correlate to its ability to sustain life.

To emphasize just how valuable the Earth is, Laughlin also estimated the worth of other planets in our solar system. Our nearest neighbor Mars costs about the same as a used car at $16,000. That's a fortune compared to Venus, which he appraised at the meager value of one cent.

Laughlin doesn't expect these numbers to have applications in the real world. Rather, he hopes they will inspire people to better appreciate the only home they know. He's not the first person to put a massive, hypothetical price tag on something just for fun. The cost of the Death Star from Star Wars has been calculated at $852 quadrillion—many times Laughlin's estimate for Earth.

Have you got a Big Question you'd like us to answer? If so, let us know by emailing us at bigquestions@mentalfloss.com.