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."

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

NASA Reveals How Living in Space for a Year Affected Scott Kelly’s Poop

NASA, Getty Images
NASA, Getty Images

When you agree to be part of a yearlong space study, you forfeit some right to privacy. In astronaut Scott Kelly’s case, the changes his body endured while spending a year at the International Space Station (ISS) were carefully analyzed by NASA, then published in a scientific journal for all to see. Kelly submitted blood samples, saliva samples, and cheek swabs. Even his poop was subjected to scrutiny.

As PBS reports, Scott Kelly’s fecal samples revealed that his gut microbiome underwent significant but reversible changes during his time in orbit. In what was surely good news for both Kelly and NASA, his gut bacteria didn’t contain anything “alarming or scary,” according to geneticist Martha Hotz Vitaterna, and it returned to normal within six months of landing on Earth.

Even after being subjected to the challenging conditions of space, “Scott’s microbiome still looked like Scott’s microbiome, just with a space twist on it,” said Vitaterna, who was one of the study’s authors.

The fecal probe was one small part of a sweeping NASA study that was just published in the journal Science, more than three years after Kelly’s return. Dubbed the Twins Study, it hinged on the results of Kelly’s tests being compared with those of his identical twin, retired astronaut Mark Kelly, who remained on Earth as the control subject.

NASA’s goal was to gain insight into the hazards that astronauts could face on proposed long-term missions to the Moon and Mars. The agency has gone to great lengths to get this information, including offering to pay people $18,500 to stay in bed for two months in order to replicate the conditions of anti-gravity.

It also explains why NASA was willing to launch unmanned rockets into space to collect samples of Kelly’s poop. On four different occasions at the ISS, Kelly used cotton swabs to pick up poo particles. When the rockets arrived to drop off lab supplies, they returned to Earth with little tubes containing the swabs, which had to be frozen until all of the samples were collected. The process was tedious, and on one occasion, one of the SpaceX rockets exploded shortly after it launched in 2015.

The study also found that his telomeres, the caps at the ends of chromosomes, had lengthened in space, likely due to regular exercise and a proper diet, according to NASA. But when Kelly returned to Earth, they began to shorten and return to their pre-spaceflight length. Shorter telomeres have a correlation with aging and age-related diseases. “Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within six months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted,” researchers wrote.

Researchers say more studies will be needed before they send the first human to Mars. Check out NASA's video below to learn more about what they discovered.

[h/t PBS]

Astronomers Want Your Help Naming the Largest Unnamed Dwarf Planet in the Universe

iStock.com/jgroup
iStock.com/jgroup

Part of the fun of becoming involved in science is naming things. Entomologists are notorious for branding new species of insects with fanciful names, like the Star Wars fans who labeled apoid wasps Polemistus chewbacca and Polemistus yoda. Sometimes scientists invite the public’s opinion, as in the 2016 petition by the UK's Natural Environment Research Council to have internet users name a polar research ship. They dubbed it Boaty McBoatFace. (That choice was overruled, and the ship is now known as the RRS Sir David Attenborough.)

Now, astronomers are looking to outsource the name of a dwarf planet. But the catch is that there’s no write-in ballot.

The planet, currently known as (225088) 2007 OR10, was discovered in 2007 in the Kuiper Belt orbiting the Sun beyond Neptune and may have a rocky, icy surface with a reddish tint due to methane present in the ice. It's bigger than two other dwarf planets in the Kuiper Belt—Haumea and Makemake—but smaller than Pluto and Eris.

The three astronomers involved in its identification—Meg Schwamb, Mike Brown, and David Rabinowitz of Caltech’s Palomar Observatory near San Diego, California—are set to submit possible names for the dwarf planet to the International Astronomical Union (IAU). They’ve narrowed the choices down to the following: Gongong, Holle, and Vili.

Gonggong, a Mandarin word, references a Chinese water god who is reputed to have visited floods upon the Earth. Holle is a German fairy tale character with Yuletide connotations, and Vili is a Nordic deity who defeated a frost giant.

The team is accepting votes on the planet’s website through 2:59 EDT on May 11. The winning name will be passed on to the IAU for final consideration.

[h/t Geek.com]

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