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.
Why did members of my family have children knowing that 1 in 4 would likely have a form of dwarfism that originated as a spontaneous mutation in my 4th great-grandfather? Why shouldn’t they have? I did not inherit the gene, but aunts, cousins and a sibling did. Despite the inconveniences (and the sometimes thoughtless comments by ignorant people) they lead lives full of meaning. My entire family, several generations’ worth, participated in early genetic studies to determine the genetic source of the condition: this knowledge led to more studies related to other joint/cartilege genetic anomalies, with hopes that someday the knowledge generated might lead to treatments for those and related disorders, perhaps even to understanding and possibly prevention.
Please note above my use of the word “spontaneous”. That means that disorders like these can arise at any time in any generation, and do. My forebear in whom the mutation occurred (no one else in his generation or the ones previous had it) migrated by himself from New England westward at the age of 16, eventually joining a land company, and later bringing his parents and other members of his family. He was a farmer and a merchant, held office and was highly respected in his community. Why shouldn’t he have had children?
Why shouldn’t the family in this story have children? We have much to learn from them and from their disorder, both about how the body functions in disorders such as theirs, and about how to live full and meaningful lives. All of us, including the people who question their choice to have children, carry the possibility of an even more insidious potential for genetic disorders, in the form of hidden defects. Should one marry a person with the same genetic misspelling, the double defect can be devastating. Are you willing to take that chance? Mind you, in such a case, the chances of passing on either the disease or carriers is 3 out of 4. In the case of the dominant gene in my family, either you have it or you don’t. Better odds.
I wish you all luck in making your decision. I’m glad my folks and my grandparents made the choice they did. And you should be, too. We are live-loving and joyful people. It’s clear the Deater descendants are too. That, by itself, is reason enough to rejoice in their existance.
I think it is interesting that some individuals think the answer is to not have children. Considering the prevalence of many different disorders, where would the tolerance be for risk? 1 in 800 people are carriers of the defective BRCA gene linked to breast and ovarian cancer. 1 in 42 boys born in the US are at risk for autism. One quarter of all adults in this country will suffer a serious mental illness. Sometimes we know the risk in time, sometimes we do not.
I had two children decades before I got the diagnosis. My son, newly married has it as well. He and his wife were discussing the issue of children and came to the same conclusion; who knows what life holds for any of us? So many, much more serious diagnosis are extremely more frequent than HSAN, yet few are considered when deciding to have children or not. I believe deciding factors should be these: Can you love any child you have? Can you afford the basic necessities? Are you physically and mentally able to deal with whatever comes along? Do you have a support system readily available to help you? Stuff happens daily with children. You need help to get through it. If you honestly can say yes to these q’s, have all the kids you want! Good luck and I wish you the best of luck in life.
I am glad to see Karen Weintraub’s article on HSAN1 and the Newcomer family. I believe each time we bring these rare disease to the attention of others that is another step towards finding a cure.
An omission in the article is the acknowledgement of the work being done by Dr. Florian Eichler at Massachusetts General Hospital. Dr. Eichler participated in all 3 studies involving the supplementation of L-serine. He was the primary researcher in the latest double-blinded study (not yet published), along with Drs. Brown, Hornemann, Oaklander, Vera Fridman, and others. We appreciate his ongoing dedication and expertise in seeking a treatment and eventual cure of HSAN1.
To all the other commentators, each of you has varying chances of having a child with birth defects or one who will grow up to have diabetes, cancer, heart disease or countless other diseases, disorders and deformities. One day, through genetic testing, you may know the exact risk factor for each of these possibilities. No human can produce a perfectly healthy baby who will always be perfectly healthy their whole lives. How dare you judge this family for living life to the fullest despite having more knowledge than most about their health futures. This is what bravery and love looks like. Your comments look like ignorance.
I certainly hope the research in curing or at least substantially slowing this illness comes soon. In the meantime, why are members of this family still having children?
Is genetic testing available for this family? Would this not be detectable by sequencing SPTLC1 to predict which members have inherited the condition?
“I’ve always prayed that my kids would not be affected”
Stop praying and stop reproducing!
I agree. why continue the line? I know there is a deep feeling of the need to continue the genetic line, but why continue a defective one.
k but why do they keep reproducing
So being aware of this genetic abnormality and knowing that it is a gamble for their future generations as to whether they will inherit the disease, the Deaters continue to multiply, in the hopes that some day science may catch up to their roll of the dice.
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