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.

Pioneering Heart Surgeon René Favaloro Is Being Honored With a Google Doodle

Dr. René Favaloro (left) pictured with colleague Dr. Mason Sones.
Dr. René Favaloro (left) pictured with colleague Dr. Mason Sones.
The Cleveland Clinic Center for Medical Art & Photography, Wikimedia Commons // CC BY 4.0

Argentinian heart surgeon René Favaloro is the subject of today’s Google Doodle, which features a sketched portrait of the doctor along with an anatomical heart and several medical tools, The Independent reports.

The renowned doctor was born on this day in 1923 in La Plata, the capital of Argentina’s Buenos Aires province, and pursued a degree in medicine at La Plata University. After 12 years as a doctor in La Pampa, where he established the area’s first mobile blood bank, trained nurses, and built his own operating room, Favaloro relocated to the U.S. to specialize in thoracic surgery at the Cleveland Clinic.

In 1967, Favaloro performed coronary bypass surgery on a 51-year-old woman whose right coronary artery was blocked, restricting blood flow to her heart. Coronary bypass surgery involves taking a healthy vein from elsewhere in the body (in this case, Favaloro borrowed from the patient’s leg, but you can also use a vein from the arm or chest), and using it to channel the blood from the artery to the heart, bypassing the blockage. According to the Mayo Clinic, it doesn’t cure whatever heart disease that caused the blocked artery, but it can relieve symptoms like chest pain and shortness of breath, and it gives patients time to make other lifestyle changes to further manage their disease.

Favaloro wasn’t keen on being called the “father” of coronary bypass surgery, but his work brought the procedure to the forefront of the clinical field. He moved back to Argentina in 1971 and launched the Favaloro Foundation to train surgeons and treat a variety of patients from diverse economic backgrounds.

Favaloro died by suicide on July 29, 2000, at the age of 77, by a gunshot wound to the chest. His wife had died several years prior, and his foundation had fallen deeply into debt, which Argentinian hospitals and medical centers declined to help pay, The New York Times reported at the time.

“As a surgeon, Dr. Favaloro will be remembered for his ingenuity and imagination,” his colleague Dr. Denton A. Cooley wrote in a tribute shortly after Favaloro’s death. “But as a man ... he will be remembered for his compassion and selflessness.” Today would have been his 96th birthday.

[h/t The Independent]

Forget Lab-Grown Meat—You Can Now Buy Lab-Grown Ice Cream

Deagreez/iStock via Getty Images
Deagreez/iStock via Getty Images

Even though “dairy-free” doesn’t necessarily mean “healthier,” it’s still a necessary disclaimer for dairy-free people who are screaming for ice cream. And between veganism, lactose intolerance, and other dietary dairy restrictions, the race is on to create an ice cream for the masses that doesn’t taste like chalk, chemicals, or sadness.

Bay Area startup Perfect Day may have just pulled ahead of the competition. Today, Fast Company reports, it released three flavors of dairy-free ice cream—Vanilla Salted Fudge, Milky Chocolate, and Vanilla Blackberry Toffee—that contain the same proteins found in cow dairy, but grown in a lab from engineered yeast and DNA. Since those proteins contribute greatly to the rich texture and taste of ice cream that we love so much, Perfect Day’s products are supposedly indistinguishable from the real thing.


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The co-founders, vegan bioengineers Ryan Pandya and Perumal Gandhi, got the idea from their experience in medicine, where fermentation is used to grow things in a lab all the time. “The two of us started scratching our heads and wondering, what if we just apply that same exact technology that’s been around for half a century to make the world’s most in-demand, highest-quality protein?” Pandya explained to Fast Company.

Their lactose-, dairy-, and gluten-free vegan ice cream, which they’ve been working on for five years, includes the dairy proteins casein and whey, as well as plant-based fats and sugar. If you're dairy-free because of a casein or whey allergy or sensitivity, you should treat this ice cream like you would any other foods containing dairy, and heed the "Contains milk protein" disclaimer on Perfect Day products.

Lab-grown dairy has environmental benefits too, considering that cows and other livestock are major culprits of greenhouse gas emissions. Pandya and Gandhi hope to sell their proteins to large-scale food manufacturers, and have teamed up with Archer Daniels Midland, an Illinois-based food processing company, to increase production.

Though it seems like a scoop or two of this ice cream might be the recipe for a perfect day, that wasn’t the inspiration behind the company’s name—the founders stumbled upon a study in which scientists discovered that cows produced more milk when listening to music, and one of the most successful songs was Lou Reed’s “Perfect Day.” “As a company on a mission to make cows, people, and the planet happier, it seemed like a perfect fit,” the website says.

Can’t wait to taste the magic? You can purchase all three flavors in a three-pint bundle for $60 here.

[h/t Fast Company]

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