Tess’s Tale: Social Media Catalyzes Rare Disease Diagnosis

Attention to the plight of families with rare diseases continues to grow this week, and provides a backdrop to another compelling tale of a family seeking a diagnosis for mysterious symptoms.

THE UNDIAGNOSED DISEASES NETWORK
The National Human Genome Research Institute’s Undiagnosed Diseases Network (UDN) just announced the UDN Gateway. This online application portal will guide patients to a growing national network of clinical sites, including six new ones and two genome sequencing centers. The Gateway replaces paper-based application to specific clinical centers for the few coveted slots.

The UDN evolved from the Undiagnosed Diseases Program, announced in September 2008. It was born to step in, for selected cases, when all available diagnostic tools can’t name a condition that is extremely rare, unknown, or an “atypical presentation” of a recognized disorder. Doing so not only helps the families and others with the same syndromes, of course, but fills in the blanks of our knowledge of the human genome. The program has evaluated 800 of 3,100 applicants since 2008, diagnosing 25%. That success rate will surely soar as human genome sequences are further annotated and gene expression patterns unraveled and connected.

THE RARE GENOMICS INSTITUTE
Although each new UDN clinical center will be taking 50 new cases a year by next summer, winning a slot is still a little like winning the lottery. But rare disease families won’t wait. And that’s where the Rare Genomics Institute comes in, a non-profit that assists families in crowdfunding the quest for a diagnosis. Their Amplify Hope Initiative started this week with ten selected families trained to crowdfund month-long campaigns. The funds will support exome sequencing to get to the bottom of each family’s diagnosis-defying medical condition.

BEYOND ICE BUCKETS

Another route to diagnosis is through social media. I lamented last summer’s Ice Bucket Challenge for ALS because it hogged the limelight. With only 12,000 cases in the U.S. ALS (Lou Gehrig’s disease) certainly fits the 200,000-patient definition of a rare disease. But association with the eponymous Yankee catapulted the disease into public awareness, as even the most remote connection to Hollywood can do.

Besides the celebrity connection, it can be hard to figure out why the national media latches on to certain families, when so many are desperate for attention. That’s why it’s so great that rare disease families reach out to and help each other. Witness the amazing “Saving Eliza” campaign of the O’Neill family of South Carolina, who are under voluntary house arrest to keep their little girl virus-free so that she can enter a gene therapy trial for Sanfilippo syndrome type A. Any national appearance of a rare disease family can help many. Coverage of the O’Neill’s story on the Today Show led to the diagnosis of at least one other child, and their more recent appearance in People — even a photo on the table of contents page and letters the next week — may identify others.

REDDIT TO THE RESCUE
The story of another little girl, Tess Bigelow, shows how social media can lead to a diagnosis, or at least to a research group working on a child’s specific gene, in just hours. I found Tess’s story on Facebook, and her dad Bo gave permission to reprint it here. It’s from his blog post, called “Answers” (edited for brevity). (Details about Tess’s illness are in Part 1 “This Isn’t Over,” and Part 2 “Not Giving Up“.

“It is night. My wife and I are emotionally drained. The Tess webpage is live and it’s getting shared. While happy that it’s gone viral, we’re reeling from how much mental effort it’s taken to make the jump. To really try. To not give up.

So there we are, reading just before bed, knackered. Barely able to mumble to each other that we should switch off the lights and hit the hay.

Then my phone buzzes on the nightstand. I pick it up.

There’s a new email in my inbox. “To whom it may concern,” it starts off. “My name is Mike Fountain and I conduct research at Baylor College of Medicine in Houston, TX. I believe I have some answers for you and Tess.”

Why does the message say “To whom it may concern,” instead of “Dear Bo and Kate?” Because we’d set up the Tess page on portlandrootsmedia.com, and all emails were sent to the general email account for that page.

So this guy doesn’t even know our names. He only knows Tess’s name.

His message continues. “I work with this gene and these symptoms and will publish our work soon. I know of other patients.”

I know of other patients.

And he gives his contact info.

I practically drop my phone out the bedroom window, frantically typing my response. We schedule a call with him.

The next day, we’re talking to him. Mike Fountain at Baylor. We can’t get our heads around this idea. We refuse to believe it. There has to be some mistake. Like, maybe we’ll tell Mike more about Tess and her symptoms, and he’ll say, “Ah. Sorry. Not the right symptoms. Not the right gene. Sorry to have bothered you.”

But that isn’t what Mike Fountain tells us. There are seven kids that he knows of. Seven other patients. Mike’s been working with a doctor at Baylor, an MD PhD, a researcher and professor of molecular and human genetics named Christian Schaaf. And their study is all about USP7. The exact gene where Tess has a mutation. (USP7 stands for ubiquitin-specific protease 7).

Mike tells us about the other seven. They are all older than Tess. The oldest is thirteen. They’re from all over the world. Some in the US, some in Europe and Asia. Two girls, five boys. They all have developmental delay and intellectual disability. Which Tess has. Several have hypotonia, or low trunk strength, which Tess also has.

Our conversation with Mike is a welcome but scary glimpse into the future. We’re about to hear what could happen with Tess. How does that 13-year-old communicate? Can she feed herself? Does she have a social life, with friends she can recognize and ask for by name? Is she happy?

Mike asks whether Tess has seizures. In the early days, when she seemed completely checked out, we’d theorized that maybe she was having seizures all the time. A subtle kind that can incapacitate somebody and you don’t even know it’s happening. We’ve had her tested for seizures a bunch. All tests have been negative. “You might want to keep an eye on that,” Mike says. “Most of the seven have seizures.”

Is Tess autistic? Man, I wish we knew. There’s no blood test for autism. Instead, doctors look at behavior and development. And Tess is so delayed with speech and social stuff that she’s never been tested. We don’t even know if she can be tested using traditional methods. “Keep an eye on that too,” Mike tells us. “Nearly all of the seven have some form of autism”.

He asks a ton of other stuff about Tess. We tell him about her visual-processing issue and our suspicions that she has an auditory processing issue as well. We talk about her loving and cheerful nature, her voracious appetite, her tendency to bite when she’s pissed off.

In the end, it’s a match. We are so thrilled that we are laughing and crying at the same time. Mike Fountain is satisfied that Tess’s symptoms and mutation line up with his patients. He’s certain that Tess belongs in this group of seven. Now there are eight.

The most mind-blowing thing about connecting with Mike Fountain and finding this match is that it only took about 12 hours. We created Tess’s page on the morning of Wednesday, August 12th, set it loose on Facebook and Twitter, and that evening, the 12th, Mike had found it and emailed us.

But Mike didn’t discover us on Facebook or Twitter. It was on Reddit, an online bulletin board that sorts content. It uses subreddits. So if you’re into My Little Pony and smoking weed, or articles that sound like they’re from The Onion but they’re real, there are subreddits. My wife and I aren’t even on Reddit. I don’t know much about it, except that most of my friends who are into science are on there a lot.

And it turns out that there’s a subreddit for genetics: r/genetics. And it’s there that Mike discovers Tess. Someone has posted the following message: “Hi r/genetics, need your help. I have a little friend who has a mutation in the USP7 gene and we can’t figure out her diagnosis despite tons of genetic testing. We’re looking for others like her – can you point us in the right direction?”

Mike Fountain isn’t on Reddit either. But a woman he shares a lab with is. And that woman shows the post to Mike and said, “Isn’t USP7 the gene you work with?”

So who posted to Reddit? Someone with the username “Oddjobpanage,” with no photo and no identifying information. We’ve since learned that Oddjobpanage is a guy in his 30s named Harry Roman, a friend of my sister and her husband. We’ve met Harry and hung out with him a few times, but it’s been years since we’ve been in touch with him. So Harry, I can’t really express how grateful we are that you shared this. That you got it to a dude who shares a lab with Mike Fountain.

Now, why didn’t I tell you this before? If Mike Fountain got in touch within 12 hours, and if we’ve known about his study for over a month, why did we wait?

We had to. From that very first email, and in every phone call since, Mike told us to keep this under our hats. He and Dr. Schaaf have been working on a paper about the seven USP7 kids, to be published on September 11th. If word got out, if I talked about it on my podcast or blog, if we splashed it all over social media, it could jeopardize the publication and even keep Mike from reaching other families. So he made us promise not to breathe a word.

The paper came out last week, in Molecular Cell. Bo’s post interprets it, explaining the disruption in control of protein recycling that likely underlies Tess’s intellectual disability, autism, and seizures. A protein called WASH must be present within a certain concentration range for adequate control of protein recycling. Bo continues:

In all this talk about the WASH protein, the final sentence shouts out to me, almost as if the rest of the article is one of those redacted CIA documents from the Cold War, where every single line is blacked out with a Sharpie, except for one sentence, the one that’s escaped the censors. The final sentence says: “… our results suggest that chemically activating WASH in these patients may have therapeutic potential.”

There may be something we can do, some type of therapy that could help Tess.

What happens now?

Mike Fountain and Dr. Schaaf are both pretty juiced. This wasn’t a one-shot deal, where they publish and hang up their guns. This is only the beginning. The syndrome doesn’t have a name yet. For now, they’re calling it “USP7-associated genetic disorder.” Tess is going to join this group of patients. She’ll be part of the next study, and it looks like everybody wants to get started right away. Mike has already put us in touch with another family, one who was part of this study. Our families have started emailing each other, comparing notes on our kids.

And we need to find more patients. This is what social media is for. Share Tess’s page. Tell everyone you know, your hairdresser. Your mail carrier. Your accountant. The guy waiting at the bus stop with you. The kid making your sandwich at the deli. Everybody you talk to and email with and Facebook with and tweet at. You never know whether a dude named Harry, who you haven’t seen in six years, who you barely know, will turn out to be the one to make it all happen.

There are families out there. Their kid has intellectual disability and low trunk strength, with signs of autism, maybe. They’re in the dark, this family. They don’t know how to help their kid. They’ve seen a million specialists, and they have no name for what’s going on. Perhaps they’ve mapped their kid’s genome and know about USP7, but they’re ready to throw in the towel. To shrug and say, well, we’ll never know. Help them find us.”

If anyone else has a story to share, please let me know. I can’t think of a better use of this blog than to connect families with each other and with researchers.