For the Deater family, it seemed like any other family reunion—a rich spread of food and children’s games—by the banks of the river. Yet, the scene at the 75th gathering on the rural land in Pennsylvania was sobering—because amid the 75 participants, some were in wheelchairs, on crutches, or wearing leg braces.

At the picnic tables, while bugs hovered, some members remained oblivious of the insistent—because they could not feel anymore. Numbed by gnarled fingers and damaged limbs, these members are victims of the devastating disease, HSAN1. It was nicknamed “Deater Disease” because majority of the affected victims in United States are traced to Alvin Deater’s line of descent.

The affected patient faces the formidable prospect of losing his legs as tissues fail to stay healthy when the nerve signals are lost. Alvin Deater’s three sons lost their legs to the disease, as did one of his great-grandsons. Some family members have undergone repeated foot surgeries to correct progressive bone deformities. For others, the fingers had folded over, leaving only stubs.

A 1915 photograph of the oldest of Alvin and Ellen Deater’s 12 children. Seven of their children would inherit the genetic mutation for HSAN1. Photo credit: Deater Family/STAT News
A 1915 photograph of the oldest of Alvin and Ellen Deater’s 12 children. Seven of their children would inherit the genetic mutation for HSAN1. Photo credit: Deater Family/STAT News

Alvin Deater, born in the late 1800s, had passed it on to seven of his 12 children. Over the years, the disease has struck at least more than 30 family members in six generations—with 16 more who are too young for the onset. There is the possibility of other family members being affected, although their symptoms are subtle and might not be noticeable.

Members of the Deater descent have set up a foundation dedicated to finding long-term treatment—and hopefully, a cure for the disease. Since its inception in 1990, the Deater Foundation, funded largely by family members along with contributions from companies, has donated over $100,000 to further HSAN1 research. They persist in seeking answers, hoping for a breakthrough.

Disease caused by one genetic spelling error

Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a dominantly inherited disease, characterised by early sensory involvement affecting pain "and temperature due to a length-dependent axonal neuropathy. Symptoms include severe shooting or burning pain in the limbs, and typically present by the late teens or second decade of life. Although not categorised as a terminal disease, HSAN1 is progressively debilitating—and many affected patients often require surgeries or the use of walking aids.

More than eight decades ago, Philadelphia doctors examined two of Alvin’s afflicted sons, Harvey and Russell, whom they believed had holes in their spines. Both were treated with radiation and suffered X-ray burns so severe that they had to have skin grafts. It was reported that their numbness did not improve, and pieces of dead bone protruded through their burnt skin for years.

In the mid-1970s, the National Institute of Health did more tests on the family members but the outcome was not favourable.

By the late 1990s, the search for answers led scientists in the US and Europe to compare the genes of Deater descendants to those without the disease mutation, and also with a few other affected families around the world. Though the mutations were slightly different, researchers managed to trace the disease to a single misplaced nucleic acid—one spelling mistake in a word billions of letters long.

The genetic glitch leaves the gene with the wrong ingredients for making an enzyme that instead, produces a toxin that eventually kills the nerve cells.

Lindsey Newcomer, 12, sits next to her father, Eric Newcomer, while Dr Anne Louise Oaklander points out the tiny mark left by a skin biopsy. Photo credit: Aram Boghosian/STAT News
Lindsey Newcomer, 12, sits next to her father, Eric Newcomer, while Dr Anne Louise Oaklander points out the tiny mark left by a skin biopsy. Photo credit: Aram Boghosian/STAT News

Start early: Tracking the disease in children

The Foundation’s board president, Eric Newcomer, could not keep his job as an electrician when his symptoms worsened. The numbness in his hands made it dangerous for him to handle hot machinery, and he has recently opted to teach.

Starting with his own children, he urged affected families to test and track their children. His teen daughters, Alexis and Lindsey Newcomer, have made two visits to Massachusetts General Hospital in Boston, for a series of balance and sensory tests.

“The sweat test was uncomfortable, but the rest was fun,” recalled Lindsey, now 13, after her first visit.

In the second round of testing, Dr Anne Louise Oaklander, a neurologist, took a 3mm bit of skin—about the size of a stud earrings—from each girl’s lower leg.

Oaklander, who has tracked the family for the past 15 years, has developed close bonding with the teens. Oaklander and her team will test if the nerves in their skin samples provide signs of disease onset.

To date, identifying the first signs has been almost impossible among researchers, and to do so would be a milestone that would shift the discussion from treatment to prevention. Usually, the patients are not aware of the symptoms until it reaches the advanced stage where they burn themselves without realising it or find themselves standing in snow without feeling the freeze.

“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.”

One laudable advancement is that scientists can now diagnose HSAN1 by looking for the disease’s characteristic toxin in the bloodstream, at least in adults. Newcomer’s girls and their cousins would help determine if early detection in children is possible.

A foul-tasting drink may promise a new beginning

Swiss biochemist Thorsten Hornemann discovered, a decade ago, that flooding the body with serine may stop the production of the toxin responsible for the nerve destruction in Deater’s members. Serine is said 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,” asserted Hornemann.

“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,” explained the scientist.

Hornemann recently completed a longer clinical trial, giving some Deater descendants serine and others a placebo for a year. 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. It might not be feasible, according to scientists, to heal badly damaged nerves and children may be more likely to benefit than adults.

Family members have to seek out a serine-only powder and dilute it a few times a day with water or juice. The Deater family knows that serine is not a cure for HSAN1—but at least, it may be able to stall disease progression.

Back in 2010, Eric Newcomer volunteered for a 10-week trial of serine back in 2010 and believed it helped. He said the shooting pains that felt like fireworks going off in his feet seemed to grow less frequent. His fingers remain gnarled and he still needs leg braces.

“It’s a gradual decline, so you figure it out as you go along,” said Newcomer, displaying the Deater descendants’ penchant toward positivity. “Whatever happens, we—my wife and I—are going to deal with it,” he said.

His daughter Lindsey, who likes singing Disney songs, echoes his attitude though she finds it gross just looking at the dressings on her dad’s infected wounds. But, she is not overly anxious or fearful about inheriting the disease.

“I just kind of know it’s there,” she said. “I’m just not going to worry about it.

Eric Newcomer’s hands have been affected by the disease that has haunted his family for generations. Photo credit: Aram Boghosian/STAT
Eric Newcomer’s hands have been affected by the disease that has haunted his family for generations. Photo credit: Aram Boghosian/STAT

The family presses on for a miracle

While the disease could have plagued the family over generations, there is one positive thing that emerges—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,” expressed Eric’s sister, Tami Murphy.

Their mother, Nancy Newcomer, shuddered in tears when faced with the grim possibility of passing on the disease. The guilt is tough, she said, and she felt it is important for family members to participate in research.

The real hope, said Bob Brown, now the chief of neurology at the University of Massachusetts Medical School, is to eliminate the disease entirely. He has been following the Deaters for nearly 40 years.

“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 has figured out how to do that in a lab dish and plans to try it on mice before testing on humans. “I would describe it as early days… promising, but early,” he said.

While Oaklander agreed that gene editing is the Deater family’s best hope, she 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,” she added. MIMS

Read more:
Synesthesia: The rare ability to experience cross-sensory sensations
Canadian doctors identify new genetic disorder in children
Baby with rare genetic disease should die with dignity, says doctors

Sources:
https://www.statnews.com/2017/08/14/rare-disease-neuropathy-deater/
http://www.deaterfoundation.org/about/about-hsan1/
http://eichler.mgh.harvard.edu/hsan1/
http://www.foxnews.com/health/2017/08/14/mysterious-disease-has-plagued-this-family-for-generations.html