NOXEN TOWNSHIP, Pa. — A quick glance around the picnic tables was enough to tell who had the genetic mutation and who didn’t. A few of the relatives gathered here before the start of their 75th family reunion fidgeted constantly, brushing away the insistent bugs. Others didn’t seem bothered at all. Their nerve damage left them unable to feel the tiny creatures.
A genetic glitch has disabled members of at least six generations of the Deater family, leaving them with gnarled fingers, damaged feet, and explosive pains. The mutation remains so rare that the relatives make up the majority of affected patients in the United States; the condition is nicknamed Deater Disease after Alvin Deater, who was born in the late 1800s and passed it on to seven of his 12 children.
Even as they anxiously watch each new generation, wondering where the symptoms will surface, the family is fighting back. For decades, Alvin’s descendants have subjected themselves to poking and prodding, blood draws and scans to help doctors better understand — and hopefully alter — their genetic fate.
As it turns out, the research could eventually help millions around the world. The nerve fiber damage that causes such misery in the Deater family looks very similar to the damage that causes people with type 2 diabetes to lose sensation in their feet, or patients undergoing chemotherapy to experience weakness in their hands.
Unlocking the secrets of Deater Disease could, perhaps, point the way to treating these other, far more common, neuropathies.
But first, those secrets must be unlocked. And that has not been an easy road.
Eighty years ago, Philadelphia doctors closely examined two of Alvin’s afflicted sons, Harvey and Russell. They believed the young men had holes in their spines and treated them with radiation. Both suffered severe X-ray burns and had to have skin grafts. Pieces of dead bone protruded through their burned skin for years.
Their numbness didn’t improve.
In the mid-1970s, family members submitted to two more rounds of testing, this time at the National Institutes of Health. That, too, failed to yield answers.
Now, Alvin Deater’s descendants are at another crossroads.
Researchers have discovered a possible treatment for the disease, formally called hereditary sensory and autonomic neuropathy type 1, or HSAN1. The therapy — an amino acid called serine — helps around the margins for adults. Theoretically, it could transform the trajectory for children who start taking it before symptoms appear.
But no one really knows whether it will be enough. Or whether there might be significant side effects.
At the start of the recent family reunion, still held on land Alvin inhabited in rural Pennsylvania, the board members of the family foundation gathered to discuss their options.
Testing the teens
Board president Eric Newcomer, whose symptoms forced him to leave his job as an electrician, wants affected families to test and track their children. He’s starting with his own.
His daughters, Alexis and Lindsey Newcomer, are just teenagers, but they’re already well-versed in the family tradition of submitting to medical tests.
Twice this summer, the girls, who both celebrated birthdays in the last week, have made the trek to Massachusetts General Hospital in Boston, a five-hour drive from their home in rural Muncy, Pa., for an array of balance and sensory tests.
“The sweat test was uncomfortable, but the rest was fun,” Lindsey, now 13, said after her first visit.
In the second round of testing, Dr. Anne Louise Oaklander, a neurologist, took a 3-millimeter bit of skin — about the size of a stud earring — from each girl’s lower leg.
Oaklander, who has grown close to the family in 15 years of tracking them, speaks to them as friends and colleagues. They’re all working together to solve the same mystery.
Oaklander and her team will see if the nerves in the skin samples from Alexis and Lindsey already show signs of trouble.
That would be a milestone: In all the decades of research, no one has yet identified the first signs of the disease. Its symptoms advance so stealthily that many people with the mutation don’t even know they have it until one day they burn themselves without realizing it, or find themselves standing in snow or on a hot beach without noticing the temperature.
“I told them, you guys are the pioneers in this next phase. I want you to volunteer to be poked and prodded and sampled.”
Being able to identify signs of the disease before symptoms arise would be huge, shifting the discussion from treatment to prevention. That’s why Eric Newcomer is so determined to keep testing his daughters as they age.
“I told them, you guys are the pioneers in this next phase,” Newcomer said. “I want you to volunteer to be poked and prodded and sampled. Whether it be for you or for me or for future generations, this is something we need to find out.”
A tiny genetic spelling error
For the Deater family, last month’s reunion was relatively small — about 75 participants. As usual, some were in wheelchairs, on crutches, or wearing leg braces. There were piles of food, children’s games, and plenty of opportunities to splash in the nearby river.
And, of course, there was an update on the family’s quest for answers.
More than 30 family members in six generations have definitely had HSAN1, with 16 more too young to yet know. Other family members were probably affected, too, but their symptoms were subtle enough that they could be ignored.
The Deater Foundation, funded largely by family members along with contributions from several companies, has donated well over $100,000 to HSAN1 research since it was founded in 1990. The foundation regularly brings together the handful of scientists from around the world who study HSAN1. Its annual newsletter goes to 200 Deater descendants.
The group’s first big success was tracking down the genetic mutation that has led to so much pain. In the late 1990s, scientists in the U.S. and Europe compared the genes of Deater descendants with the mutation to those without, and did the same with a few other affected families around the world.
The mutations were slightly different, but researchers pinned the problem to a single misplaced nucleic acid — one spelling mistake in a word billions of letters long.
The spelling mistake leaves the gene with the wrong ingredients for making an enzyme that helps nerve cells function properly. Instead, the gene produces a toxin that eventually kills the nerve cells, leading to loss of feeling and muscle tone — and eventually much worse.
All three of Alvin Deater’s sons lost both of their legs to the disease, as did one of his great-grandsons — for the same reason many diabetics suffer amputations: Tissue can’t stay healthy when the nerve signals are lost. The body requires nerves to stay alive; without them, bones get reabsorbed, blood vessels don’t work correctly, cells die, and infection can set in.
Some family members have undergone repeated foot surgeries to correct progressive bone deformities. In others, once their fingers folded over, the useless parts were absorbed by the body, leaving only stubs.
Scientists can now diagnose HSAN1 by looking for the disease’s characteristic toxin in the bloodstream, at least in adults. Research on the Newcomer girls and their cousins will help determine if it’s detectable in children, too.
Finding hope in a foul-tasting drink
About a decade ago, Swiss biochemist Thorsten Hornemann and his colleagues figured out that flooding the body with serine, one of the normal building blocks of proteins, stops most production of the toxin that kills off nerves in HSAN1 patients. Serine also appears to help patients produce the proper enzymes.
Since serine is made by the body — it’s one of the 21 building blocks needed to make proteins — it should be safe to take, even at relatively high levels, Hornemann said.
Serine is not a pharmaceutical; it’s a nutritional supplement. That means health food stores are loaded with serine products — but most contain other additives, like alanine, which would be like adding fuel to the HSAN1 fire, Hornemann said.
Instead, family members have to seek out a serine-only powder and dilute it a few times a day with water or juice.
Some family members hate the taste; others feel like Eric Newcomer, who said “I’ve had worse.”
He participated in a 10-week trial of serine back in 2010 — and said he believed the serine helped.
The shooting pains that felt like fireworks going off in his feet seemed to grow less frequent. His fingers are still gnarled, though, and he still needs leg braces. He hopes the serine may have slowed the progression of his disease, but, of course, he doesn’t know what he would be like if he hadn’t taken it.
“It’s a gradual decline, so you figure it out as you go along,” said Newcomer, displaying the Deater descendants’ penchant toward positivity.
He was an electrician until the numbness in his hands made it dangerous for him to handle hot machinery. He moved into a supervisory role, and more recently into teaching. “Whatever happens, we’re — my wife and I — we’re going to deal with it,” he said.
His daughter Lindsey, a chatty seventh-grader who likes singing Disney songs, has the same attitude. She finds it gross when the dressings on her dad’s infected wounds need to be changed. But she’s not much bothered by HSAN1, or the possibility that she might have inherited it.
“I just kind of know it’s there,” she said.“I’m just not going to worry about it.”
“I just kind of know it’s there. I’m just not going to worry about it.”
Hornemann, along with his colleagues at Mass. General, recently completed a longer clinical trial, giving some Deater descendants serine and others a placebo for a year. Although he has not yet published his results, he said they showed some — but not overwhelming — improvements.
The amino acid, he said, seems to work better in mice than in adults — though there is still a chance it could make a significant difference to children with Deater Disease.
A family looks to the future for cures
One good thing about having a genetic disease that also afflicts two dozen relatives: family support.
“When you’re worried about the kids or your own future, just to have that inspiration to tap back into is pretty priceless,” said Tami Murphy, who’s Eric’s sister.
Their mother, Nancy Newcomer, burst into tears when asked about passing on HSAN1.
The guilt is tough, she said.
“I’ve always prayed that my kids would not be affected, but nothing can be accomplished if someone isn’t willing to say, ‘OK, test me.’”
That’s why it’s so important to her to see so many family members participating in research. “I’ve always prayed that my kids would not be affected, but nothing can be accomplished if someone isn’t willing to say, ‘OK, test me,’” she said.
While some family members feel that serine has helped them, scientists say it’s just not feasible to heal nerves that have already been badly damaged. That’s why children are more likely to benefit than adults.
And it’s why Eric Newcomer wants to start both his girls on serine now, though they don’t have any obvious symptoms. If they do have the disease, he hopes to forestall its progression. If they don’t, he hopes they’ll further research in the field by showing that serine is safe for teens to take.
Last week, Newcomer, who serves as president of the Deater Foundation, sent a letter to his cousins whose children are at risk for HSAN1, explaining that they all could participate in the research, too.
But everyone in the Deater family knows that serine is not a cure for HSAN1. At best, it may be able to stave off progression. The day someone with the mutation stops taking the drug, their body will start producing the toxin again.
Bob Brown, now the chief of neurology at the University of Massachusetts Medical School, has been following the Deaters for nearly 40 years. He said his real hope is to eliminate the disease entirely, through gene therapy.
“We’re interested in trying to silence the mutant gene, so it can’t even make the protein to make the toxic substance,” he said.
He’s figured out how to do that in a lab dish and soon plans to try it in mice. After that, he’ll try people. “I would describe it as early days … promising, but early,” he said.
Oaklander agreed that gene editing is the Deater family’s best hope — but noted it’s likely that someone else, somewhere else, will eventually end up with the same genetic spelling mistake.
“Ideally we’d like to wipe out the disease for future generations,” she said. “But there are always going to be future generations.”
Correction: An earlier version of this story failed to give proper credit to Thorsten Hornemann’s colleagues.
I bought the digital scale from amazon(kitchen use) for around $15, and serine from purebulk.com. I dissolve the amount of serine I can tolerate into warm water and drink it after the first bite of breakfast. Without having any food in my stomach before taking serine, I would feel nauseous. I’m not able to tolerate the recommended dose 200mg/kg or 400mg/kg. Even with just the half dose 100mg/kg, it gives side effect to my brain and intestine. I would feel too much energy in my head, feel like 1000 watts of light ball “shine” on the back of my head. I would feel my brain is going to explode. It is very scary, so I take serine in a very low dose, currently only 1.6g. (My weight is 47kg) It still helps, muscle strength, in a minimal way though…The side effect issues maybe just me, I heard most of hsan1 patients tolerate it fine.
I am sorry that you have hsan1, the pain is really no fun; but have a diagnosis confirmed make you feel “settled.” I have nerve and muscle problem for more than 35 years, when the genetic test and lab results came back to confirm this hsan1 diagnosis, I felt the culprit is finally captured. It is a great great comfort.
I was recently diagnosed with HSAN type 1 asfter 18 years of terrific Neuropathy. I saw any new doctor I could find looking for help, relief, and a possible cure, at least an end to the pain. When I was tested my doctor was looking for something far worse, I think, so this was a relief…briefly. Last month both of my adult children were tested. Each believed he or she had it though neither had symptoms. It turned out only my son was affected. I don’t know who passed it to me as I can’t think of anyone in my family who exhibited many of the symptoms but my father’s father died before I would have known. After thinking on it, my father had to be the one to pass it to me. He died even younger than his father. He was 57 and had lung cancer. His sister also probably had it, although I didn’t know her very well. My son and I are starting on the Serine. I wondered if there are any tips anyone can give me on best place 5o buy it and best way to take it, eg time of day, all at once or in 3’s. Suggestion for what to mix it with. I appreciate all serious answers. Thanks!
None of my family or relatives have HSAN1, but I do, and DNA tests show that my parents are my biological parents, that makes me the first person to carry this mutation in my entire family. What I want to say is that regardless whether disease affected people decide to have offspring or not, genetic mutation could happen anywhere, it is just part of nature.
I am from Taiwan. I admire Deater family for deciding to take action. They established a foundation, do the fundraising, formed and joined a research team, created the website , educate people about the cause of this condition, invite scholars, scientists, and doctors from all over the world to discuss about the pathogenesis and possible treatment or cure.
HSAN1 does not only happen in one family or in one country but worldwide, multiple continents, affecting estimated thousands of people.
Because of their initiative and involvement, I have seen people whose disease-caused gene for their nerve problem remain unknown for years, now found, others’ neuromuscular symptoms were mysteries to their physicians before, now clear. HSAN1 is such a rare disease that even a very experienced neurologist may not be familiar with it enough to detect it quickly. What the foundation does is raise the public awareness which benefits the patients and doctors. Individuals affected with disease now for the first time in their life see reversal from their deteriorating conditions because of serine. They are thrilled, and finally see the light at the end of the tunnel. What the Deater family do is inspirational and admirable that helps a lot of people, including me.
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