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."

Know of something you think we should cover? Email us at tips@mentalfloss.com.

12 Intriguing Facts About the Intestines

When we talk about the belly, gut, or bowels, what we're really talking about are the intestines—long, hollow, coiled tubes that comprise a major part of the digestive tract, running from the stomach to the anus. The intestines begin with the small intestine, divided into three parts whimsically named the duodenum, jejunum, and ileum, which absorb most of the nutrients from what we eat and drink. Food then moves into the large intestine, or colon, which absorbs water from the digested food and expels it into the rectum. That's when sensitive nerves in your rectum create the sensation of needing to poop.

These organs can be the source of intestinal pain, such as in irritable bowel syndrome, but they can also support microbes that are beneficial to your overall health. Here are some more facts about your intestines.

1. The intestines were named by medieval anatomists.

Medieval anatomists had a pretty good understanding of the physiology of the gut, and are the ones who gave the intestinal sections their names, which are still used today in modern anatomy. When they weren't moralizing about the organs, they got metaphorical about them. In 1535, the Spanish doctor Andrés Laguna noted that because the intestines "carry the chyle and all the excrement through the entire region of the stomach as if through the Ocean Sea," they could be likened to "those tall ships which as soon as they have crossed the ocean come to Rouen with their cargoes on their way to Paris but transfer their cargoes at Rouen into small boats for the last stage of the journey up the Seine."

2. Leonardo da Vinci believed the intestines helped you breathe.

Leonardo mistakenly believed the digestive system aided respiratory function. In 1490, he wrote in his unpublished notebooks, "The compressed intestines with the condensed air which is generated in them, thrust the diaphragm upwards; the diaphragm compresses the lungs and expresses the air." While that isn't anatomically accurate, it is true that the opening of the lungs is helped by the relaxation of stomach muscles, which does draw down the diaphragm.

3. Your intestines could cover two tennis courts ...

Your intestines take up a whole lot of square footage inside you. "The surface area of the intestines, if laid out flat, would cover two tennis courts," Colby Zaph, a professor of immunology in the department of biochemistry and molecular biology at Melbourne's Monash University, tells Mental Floss. The small intestine alone is about 20 feet long, and the large intestine about 5 feet long.

4. ... and they're pretty athletic.

The process of moving food through your intestines requires a wave-like pattern of muscular action, known as peristalsis, which you can see in action during surgery in this YouTube video.

5. Your intestines can fold like a telescope—but that's not something you want to happen.

Intussusception is the name of a condition where a part of your intestine folds in on itself, usually between the lower part of the small intestine and the beginning of the large intestine. It often presents as severe intestinal pain and requires immediate medical attention. It's very rare, and in children may be related to a viral infection. In adults, it's more commonly a symptom of an abnormal growth or polyp.

6. Intestines are very discriminating.

"The intestines have to discriminate between good things—food, water, vitamins, good bacteria—and bad things, such as infectious organisms like viruses, parasites and bad bacteria," Zaph says. Researchers don't entirely know how the intestines do this. Zaph says that while your intestines are designed to keep dangerous bacteria contained, infectious microbes can sometimes penetrate your immune system through your intestines.

7. The small intestine is covered in "fingers" ...

The lining of the small intestine is blanketed in tiny finger-like protrusions known as villi. These villi are then covered in even tinier protrusions called microvilli, which help capture food particles to absorb nutrients, and move food on to the large intestine.

8. ... And you can't live without it.

Your small intestine "is the sole point of food and water absorption," Zaph says. Without it, "you'd have to be fed through the blood."

9. The intestines house your microbiome. 

The microbiome is made up of all kinds of microorganisms, including bacteria, viruses, fungi, and protozoans, "and probably used to include worm parasites too," says Zaph. So in a way, he adds, "we are constantly infected with something, but it [can be] helpful, not harmful."

10. Intestines are sensitive to change.

Zaph says that many factors change the composition of the microbiome, including antibiotics, foods we eat, stress, and infections. But in general, most people's microbiomes return to a stable state after these events. "The microbiome composition is different between people and affected by diseases. But we still don't know whether the different microbiomes cause disease, or are a result in the development of disease," he says.

11. Transferring bacteria from one gut to another can transfer disease—or maybe cure it.

"Studies in mice show that transplanting microbes from obese mice can transfer obesity to thin mice," Zaph says. But transplanting microbes from healthy people into sick people can be a powerful treatment for some intestinal infections, like that of the bacteria Clostridium difficile, he adds. Research is pouring out on how the microbiome affects various diseases, including multiple sclerosis, Parkinson's, and even autism.

12. The microbes in your intestines might influence how you respond to medical treatments.

Some people don't respond to cancer drugs as effectively as others, Zaph says. "One reason is that different microbiomes can metabolize the drugs differently." This has huge ramifications for chemotherapy and new cancer treatments called checkpoint inhibitors. As scientists learn more about how different bacteria metabolize drugs, they could possibly improve how effective existing cancer treatments are.

This 3D-Printed Sushi is Customized For You Based on the Biological Sample You Send In

Open Meals
Open Meals

Many high-end restaurants require guests to make a reservation before they dine. At Sushi Singularity in Tokyo, diners will be asked to send fecal samples to achieve the ideal experience. As designboom reports, the new sushi restaurant from Open Meals creates custom sushi recipes to fit each customer's nutritional needs.

Open Meals is known for its experimental food projects, like the "sushi teleportation" concept, which has robotic arms serving up sushi in the form of 3D-printed cubes. This upcoming venture takes the idea of a futuristic sushi restaurant to new extremes.

Guests who plan on dining at Sushi Singularity will receive a health test kit in the mail, with vials for collecting biological materials like urine, saliva, and feces. After the kit is sent back to the sushi restaurant, the customer's genome and nutritional status will be analyzed and made into a "Health ID." Using that information, Sushi Singularity builds personalized sushi recipes, optimizing ingredients with the nutrients the guest needs most. The restaurant uses a machine to inject raw vitamins and minerals directly into the food.

To make things even more dystopian, all the sushi at Sushi Singularity will be produced by a 3D-printer with giant robotic arms. The menu items make the most of the technology; a cell-cultured tuna in a lattice structure, powdered uni hardened with a CO2 laser, and a highly detailed model of a Japanese castle made from flash-frozen squid are a few of the sushi concepts Open Meals has shared.

The company plans to launch Sushi Singularity in Tokyo some time in 2020. Theirs won't be the first sushi robots to roll out in Japan: The food delivery service Ride On Express debuted sushi delivery robots in the country in 2017.

[h/t designboom]

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