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NIH Hosts Rare Disease Day; Countries Around World Stage Similar Events Marking Significance of 7,000 Individually Rare Diseases That, When Taken Together, Afflict Over 400 Million People; Many Are Grievously Affected Children with Genetic Diseases

On Thursday, February 28, 2019, the US National Institutes of Health (NIH) hosted its ninth annual Rare Disease Day (RDD) event, which included a feature address b NIH Director Francis Collins, MD, PhD, and is held to raise awareness, report progress, and speed advances for patients afflicted by the estimated 7,000 “rare diseases” that exist throughout the world. Approximately 80 percent of these rare diseases are genetic in origin, with more than half affecting children, and many being life-threatening. Although rare when viewed individually, these diseases--such as giant axonal neuropathy (GAN) (50 affected families in world) which the little girl Amber (https://www.friendsatnih.org/hope-for-amber/) (https://childrensinn.org/amber/) in the photo has (see much larger version of this photo at end of story), Fabry disease (8,000 in US), Niemann-Pick Type C (2,200 in US), hemophilia (18,000 in US), ALS (Lou Gehrig’s disease) (20,000 in US), cystic fibrosis (30,000 in US), and sickle cell anemia (100,000 in US)-- affect an estimated 400 million people around the world. These numbers can be contrasted with those for some common diseases such as type 2 diabetes (21 million in US), Alzheimer’s (5.7 million in US), invasive breast cancer in women (predicted 270,000 new cases expected to be diagnosed in 2019 in US), malaria (212 million cases worldwide in 2015), and tuberculosis (2 billion infected worldwide). (Editor's Note: In the US, rare diseases are defined as those affecting 200,000 or fewer people in the country of over 325 million.)

Unfortunately, the relatively small number of people affected by each individual rare disease means that these rare diseases are often ignored by major pharmaceutical companies and also tend to be little known by the general public. As a consequence, research progress can be particularly slow. The annual world RDD events, which have been held since the inaugural such event in February 29, 2008, are intended to help raise awareness and speed research progress so that help can be brought to these struggling patients as quickly as humanly possible.

Thursday’s all-day RDD event at the NIH, in Bethesda, Maryland, just outside Washington, DC, was attended by over 1,000 participants (almost double the attendance at last year’s NIH RDD), including patients, their families, physicians, and organizations that are attempting to raise funds for rare disease research and to aid patients in any ways they can. Many of these organizations are run by parents and other family members of those with rare diseases. This year’s NIH RDD attendees came from almost every state in the union, as well as a number of other countries.

In addition to many related RDD events being held throughout the United States, almost 100 similar events were held around the world last week—including events in Iran, Malta, Taiwan, Canada, South Africa, Kenya, Brazil, and many, many other countries.

Among some of the very public recognitions of RDD in the United States were the inclusion of a 16-page “Rare Diseases” insert in the February 28, 2019 edition of the USA Today national newspaper, the evening lighting of New York City’s Statue of Liberty in RDD colors green, pink, light blue, and purple, and the projection of rare disease patient images on Boston’s City Hall (https://www.bostonglobe.com/business/2019/02/28/event-aims-highlight-rar...).

The NIH RDD meeting opened with a heart-warming video greeting from rare disease groups from all over the world and this was followed by opening remarks from Christopher Austin (https://ncats.nih.gov/director), MD, Director of the NIH’s National Center for Advancing Translational Sciences (NCATS) and from James Gilman, MD, CEO of the NIH’s Clinical Center. There was also an informative progress update from Anne Pariser (https://ncats.nih.gov/staff/pariserar), MD, Director of the NIH’s Office of Rare Disease Research (ORDR).

ZEBBIE AWARDS ANNOUNCED

Dr. Pariser then announced the top three winners of the Zebbie Award competition, which was new to RDD this year. The aim of the new Zebbie Award competition, called the “Rare Diseases Are Not Rare! Challenge,” was to help address the misconceptions that exist about rare diseases by seeking creative ways to help raise awareness about rare diseases and the need for expanded research and patient support. Dr. Pariser said that the response to the challenge was nearly 50 submissions, which included posters, videos, poems, and more.

First Place of $3,000 went to Nancy Netherland for “Unicorns and Super Heroes Are Rare — Rare Diseases Are Not.” Nancy’s entry incorporated designs for posters, social media posts, presentation materials, and infographics depicting unicorns, superheroes, and other mythical figures, combined with brief rare disease facts and humor to show how common rare diseases really are.

Second place of $1,500 went to Christina Loccke, Lindsey Bergstrom, and Sarah Theos for “In the Land of Rare Disease,” a video narrated by a child afflicted with the rare disease localized scleroderma. The video includes original artwork from children with rare diseases, combined with brief facts about rare diseases.

Third Place of $500 went to Matthew Beardall, Sami Assaf, and Naveen Upender for “Unicus,” a video compilation of “person-on-the-street” interviews with random community members in Bethesda, Maryland. “Unicus,” which is Latin for unique, provides rare disease education through informal conversations.

The highly impressive winning entries were on display on two big video screens throughout the day at NIH RDD.

"OUR CHILDREN ARE OUR MASTERPIECES" BEYOND THE DIAGNOSIS PROJECT USES ART TO ADVANCE RARE DISEASE PROGRESS

The Zebbie Award presentations were followed by Patricia Elaine Weltin’s unveiling of a beautiful new portrait of a rare disease patient, as part of Patricia’s incredible effort to raise the awareness of rare diseases through art.

Patricia is the parent of two daughters with Ehlers-Danos syndrome and she is the Founder & CEO of Beyond the Diagnosis (https://www.beyondthediagnosis.org/), an organization that “unites art and science to inspire research and innovation of treatments for people living with orphan and neglected diseases.”

In her introductory remarks, Patricia noted that her organization’s efforts to communicate and raise awareness of rare diseases through art have grown by over 500% in the last three years.

The Beyond the Diagnosis traveling art exhibit debuted at Brown University’s Alpert Medical School in February 2015 in honor of World Rare Disease Day.

The effort was described to over six million viewers of CBS Sunday News in August 2016 in a story titled “Putting a Face on Rare, Incurable Diseases” (https://www.cbsnews.com/news/putting-a-face-on-rare-incurable-diseases/).

The traveling exhibit has been in many major health facilities since its debut. It was at the Mayo Clinic in Rochester Minnesota for three months last summer (https://individualizedmedicineblog.mayoclinic.org/2018/06/07/the-human-g...) and it is currently on display through April 1, 2019, at the Broad Institute in Cambridge, Massachusetts (https://www.rarediseaseday.org/event/united-states/3175).

In addition to the traveling exhibits, Patricia has now published three beautiful volumes that provide almost 100 patient portraits, with a description of each patient written by a family member---usually the mom or dad--and a rigorous description of the patient’s disease. The current volume, #3, carries a moving quote from Henry David Thoreau on its cover: “It’s not what you look at that matters. It’s what you see.”

Patricia noted that the prestigious scientific journal The Lancet (Child & Adolescent Health) recently recognized the significance of the Beyond the Diagnosis effort with an article titled “Artists Adopt Orphan Diseases,” in its October 2018 issue (https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(18)30290-6/fulltext).

One quote from that moving article is the following: “What has astonished Weltin is how emotive the portraits are. ‘There are not that many projects out there that are this heart-warming, this moving, and this powerful,’ she said on the phone. Describing an opening at the Mayo Clinic, she spoke of an entire room of doctors, researchers, families, and artists moved to tears. Testimonies on the website confirm the power of putting a real child’s face to an otherwise faceless disease: ‘Here’s a real person who deals with the disease day in and day out. As a scientist, the portraits humanize the science and make it more relevant. They’re incredibly motivating and inspiring,’ says Dr Anne G from the Broad Institute.”

Patricia ended her remarks by saying that the Beyond the Diagnosis art exhibits and volumes, “capture the hearts of everyone who sees them.”

“Our children are our masterpieces,” Patricia said.

UNVEILING PORTRAIT OF AMBER

The newest Beyond the Diagnosis portrait, by artist Jota Leal, is of 9-year-old Amber, who has the rare neurological disease giant axonal neuropathy (GAN). Beautiful Amber was sitting in the front row of the NIH RDD audience with her parents Leticia and Mieguel (https://www.friendsatnih.org/hope-for-amber/) (https://childrensinn.org/amber/). Amber was beautifully dressed and wearing a sparkling pair of new shoes. The family lives in San Jose, California.

GAN (https://ghr.nlm.nih.gov/condition/giant-axonal-neuropathy) is a rare inherited genetic disorder. The majority of children with GAN will begin to show symptoms of the disease sometime before five years of age. The typical symptoms of GAN are clumsiness and muscle weakness that progresses from a “waddling gait” to a pronounced difficulty in walking.

Additional symptoms include numbness or lack of feeling in the arms and legs, seizures, nystagmus (rapid back and forth movement of the eyes), and impaired cognitive development.

A characteristic sign of the disease is dull, tightly curled hair that is markedly different from the parents’ in color and texture. GAN is inherited in an autosomal recessive pattern, which means that both parents of a child with GAN have to carry a copy of the mutated gene. Parents, typically though, will show no signs of the disease. Currently, most GAN patients do not live past their 20’s.

Amber is currently the tenth person in the world to begin participating in a gene therapy clinical trial for GAN. The NIH-sponsored phase I clinical trial is underway to test a potential treatment for GAN using viral-mediated GAN gene replacement (https://clinicaltrials.gov/ct2/show/NCT02362438). This trial marks the first-ever instance of intrathecal (IT) adeno-associated viral (AAV) gene transfer in humans.

The leader (principal investigator) of this trial is Carsten Bonnemann, MD, Chief, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH’s National Institute of Neurological Disorders and Stroke (NINDS) (https://www.genome.gov/27549051/bonnemann-group/).

At the end of Patricia’s remarks, little Amber, using her walker, and her family walked up to the stage for the unveiling of the new portrait. When the veil was removd and everyone saw the magnificent portrait, there was not a dry eye in the 1,000-person house. The amazing photo that accompanies this article brilliantly captures the awesome significance and dramatic human emotion of this magic moment more than words ever could (see large version of this photo at end of story).

Art can indeed change the world.

For additional information on the Beyond the Diagnosis traveling art exhibit and/or the Beyond the Diagnosis volumes, you may contact Patricia Elaine Weltin at Beyond the Diagnosis, 1005 Main Street #8107, Pawtucket, RI 02860, Phone: 401-434-0052; Message 401-487-3012 (http://www.beyondthediagnosis.org).

REMARKS BY NIH DIRECTOR FRANCIS COLLINS

The NIH RDD event featured a mid-morning keynote address by NIH Director Francis Collins, MD, PhD, who was the leader of the Human Genome Project, and who has intimate first-hand experience in efforts to understand and treat rare diseases. Much earlier in his career, in 1989, Dr. Collins spearheaded the successful effort to identify the gene (CFTR) that is mutated in cystic fibrosis. More recently, in 2003, Dr. Collins led a research effort that determined that a single base change mutation (C->T) in the LMNA gene for the lamin A protein causes Hutchinson-Guilford progeria syndrome (HGPS) (a similar effort yielding the same result was completed at the same time in France).

HGPS is an extremely rare disease of dramatically accelerated aging that has a prevalence of approximately just 350 children living with the disease at any one time in the entire world.

The lamin A protein plays an important role in determining the shape of the nucleus within cells. It is an essential supporting component of the nuclear envelope, which is the membrane that surrounds the nucleus. The HGPS condition greatly increases the chances of having a heart attack or stroke at a young age.

There was already significant knowledge of the biochemistry of lamin A and, based on this knowledge, early thoughts were that a certain class of existing anti-cancer drugs (farnesyltransferase inhibitors—FTIs) might hold therapeutic potential for HGPS. And, in fact, a clinical trial of an FTI in HGPS, which began in 2007 and was completed in 2012, did show modest improvement in some HGPS symptoms, and extended lifespan by at least five years.

But still, despite this remarkable early success, as is so often the case, a true cure is difficult to achieve and has remained elusive. Dr. Collins comments insightfully on the status of HGPS research in a 2016 article in Circulation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101939/), in which the disappointing results of a triple-combination-drug trial for HGPS were reported.

It should be noted, however, that two reports on the development and possible success of CRISPR/Cas9 editing approaches in treating mouse models of HGPS have just been reported on February 18, 2019 in Nature Medicine (https://www.nature.com/articles/s41591-018-0338-6) (https://www.nature.com/articles/s41591-019-0343-4).

In his RDD remarks, Dr. Collins expressed great optimism about the prospects for progress on rare diseases in general. He noted that awareness of them is increasingly growing, demonstrated in part by the record turnout at the current event and by the responses he has observed in Congress.

He said that we are at a “remarkable moment” when the trajectory of progress and forward motion on rare diseases is ascending. We are moving in “exciting directions,” he said, but “we still have a long way to go.”

He emphasized the significant progress that has been made with gene editing techniques such as CRISPR/Cas9 and the hope that these techniques hold out for correcting genetic defects at the very heart of the disorders, namely the misspelling of a gene.

These editing techniques offer the long-dreamed-of prospect of being able to fix multiple diseases with the same basic approach, Dr. Collins said, and the importance of developing such an ability “cannot be overstated.”

The Director noted that, in early 2018, the NIH announced plans to allocate approximately $190 million over six years to its Somatic Cell Genome Editing (SCGE) program (https://commonfund.nih.gov/editing). At the time of the SCGE announcement, Dr. Collins said that “Genome editing technologies such as CRISPR/Cas9 are revolutionizing biomedical research. The focus of the SCGE program is to dramatically accelerate the translation of these technologies to the clinic for treatment of as many genetic diseases as possible.”

Funding for the SCGE program will come from the NIH Common Fund (https://commonfund.nih.gov/), which funds programs that address emerging scientific opportunities and pressing challenges in biomedical research that no single NIH Institute or Center can address on its own, but are of high priority for the NIH as a whole.

The Common Fund is a unique resource at NIH, functioning as a “venture capital” space where high-risk, innovative endeavors with the potential for extraordinary impact can be supported. Common Fund programs are short-term, goal-driven strategic investments, with deliverables intended to catalyze research across multiple biomedical research disciplines.

Dr. Collins said that significant progress has recently been made in gene editing approaches to correct the single base change mutation that is at the root of sickle cell anemia disease and he tantalizingly suggested that the audience should pay close attention to 60 Minutes shows in the upcoming months to view news about this progress.

He also encouraged everyone to read his biweekly (Tues/Thurs) Director’s blog (https://directorsblog.nih.gov/), noting he had this very day (February 28, 2019) posted a pertinent item on the rare disease Job’s syndrome. That item is titled “From the Front Lines of Rare Disease Research (https://directorsblog.nih.gov/2019/02/28/thoughts-from-the-front-lines-o...).

Job’s syndrome (https://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome) is also known as autosomal dominant-hyper-IgE syndrome (AD-HIES). There is currently no cure for this rare genetic disease, which impairs the immune system and affects multiple parts of the body.

Dr. Collins closed by giving everyone some words of advice that one of his HGPS patients (Sam Burns) had lived by, including to be OK with what you cannot do, to surround yourself with those who care for you, and to constantly move forward.

FOUR MAJOR SESSIONS

The NIH RDD also featured four major hour-long sessions on different topics of great importance in the area of rare diseases.

The first session was on “The Collective Research Model with the NIH Rare Disease Clinical Research Network (RDCRN).” In this session, panelists--including Michael Shy, MD, Principal Investigator, Inherited Neuropathies Consortium and Director, Division of Neuromuscular Disease and Division of Neurogenetics, Department of Neurology, University of Iowa; and Seema Aceves, MD, PhD, Principal Investigator, Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR), Professor of Pediatrics & Medicine, UC-San Diego, and Director, Eosinophilic Gastrointestinal Disorders Clinic, Rady Children’s Hospital, San Diego---discussed the importance of collaborative research approaches for rare diseases and shared case studies and illustrative examples from the RDCRN, which integrates academic investigators, patient groups, trainees, NIH scientific staff, and others to accelerate rare disease research. This session was moderated by Tina Urv, PhD, Program Director, ORDR, NCATS, NIH.

The second session was on “The Power of Patients—Harnessing Quality Registries to Understand Your Rare Disease.” This session emphasized that an essential step in improving the diagnosis and treatment of a rare disease is to establish an understanding of the disease’s natural history. Natural history studies often provide foundational information for clinical research and drug development programs, and these studies often rely on active partnerships with patient organizations. Panel members--including Forbes Denny Porter, MD, PhD, Clinical Director & Senior Investigator, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; and Jeanine D’Armiento, MD, PhD, Professor of Medicine & Anesthesiology, Director of the Center for LAM and Rare Lung Disease, Columbia University Medical Center, and Chair, Board of Directors, Alpha-1 Foundation--discussed their experiences in developing registries to understand rare diseases and in using natural history data to advance care for rare disease patients. This session was moderated by Eric Sid, MD, MHA, Presidential Management Fellow, ORDR, NCATS, NIH.

The third session focused on “Success Factors for Rare Cancer Research—Building Strong Foundations.” Panelists--including Karlyne Reilly, PhD, Director, Rare Tumor Initiative, Center for Cancer Research, NCI; and Jack Welch, MD, PhD, Medical Officer, International Rare Cancers Initiative, Center for Global Health, NCI--discussed similarities and differences in the challenges researchers face in rare cancers, as compared to those faced in other rare diseases. Experts from the NIH’s National Cancer Institute (NCI) and leading rare cancer advocates described their efforts to coordinate research both nationally and internationally, as well as different models of success for rare cancer advocacy and the role of social media in building rare cancer communities and recruiting patients for studies. This session was moderated by Abby Sadler, PhD, Director, My Pediatric and Adult Rare Tumor (MyPART) Network, Center for Cancer Research, NCI.

The final hour-long session was titled “No Disease Left Behind, No Patient Left Behind,” and opened with remarks by Philip John Brooks, PhD, Program Director, ORDR, NCATS, NIH. Then panelists--including John Tisdale, MD, Chief, Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, NIH; Helen Hemley, Program Manager, CARE Research Center, Massachusetts General Hospital; Mandy Mansaray, RN, MA, Program Coordinator, Clinical Research Volunteer Program, Office of Patient Recruitment, Clinical Center, NIH; and Tesha Samuels, a rare disease patient--acknowledged that new technologies such as gene editing and genome therapy have potentially broad implications for many rare diseases, but noted that, for clinical trials, there are practical challenges that need to be addressed to ensure that these technologies are accessible to all patients who might benefit from them. The moderator of this session was Jonathan Jackson, PhD, Center Director, Community Access, Recruitment, and Engagement (CARE) Research Center, Massachusetts General Hospital.

THE CHILDREN’S INN AT NIH: "A PLACE LIKE HOME"

The closing presentation of the day was delivered by Jennie Lucca, MSW, CEO of The Children’s Inn at NIH (https://childrensinn.org/), and, interestingly, a native of Alaska who had earned her MSW at The Catholic University of America in Washington, DC. Jennie’s moving presentation focused on the children who are being helped by NIH research and who stay for periods of time with their families at The Children’s Inn.

The Children’s Inn at NIH is a residential “Place Like Home’’ for families with children participating in leading-edge research studies at the NIH. The NIH Clinical Center is the nation’s premier biomedical research hospital, providing an opportunity for Children’s Inn residents to be partners in advancing medical discoveries and improving the health of people all over the world. While the NIH takes care of the child’s medical needs, The Inn tends to the child’s heart, soul, and spirit.

Some of the history of this phenomenal, almost 30-year-old facility is outlined on its web site and is reproduced below.

“In the early 1980s, Dr. Philip Pizzo, then Chief of Pediatrics at the National Cancer Institute, noticed that families often congregated in the waiting room of the NIH Clinical Center after treatment instead of returning to the isolation of the hotel rooms where they were staying. He envisioned a supportive residence where families could stay without enduring the hardships and expense of living in a hotel. His vision was to build a convenient place with a home-like environment where families could stay together, for free, while their children were undergoing treatment at the National Institutes of Health.”

“The NIH donated two acres of land and Merck & Co., Inc. provided $3.7 million to build this “place like home.” A dedicated group of congressional spouses formed The Friends of The Children’s Inn and raised $2 million to furnish the residence. Dr. Pizzo, the congressional spouses, and several key individuals and organizations worked together to make this dream a reality and The Children’s Inn at NIH opened its doors in June of 1990 with 37 sleeping rooms.”

Today, The Children’s Inn has many more sleeping rooms, and has housed over 15,000 patients in its almost 30 years of wonderful existence.

In her presentation, Jennie noted that one young patient (Abram) had been asked what his favorite thing was about The Children’s Inn. Abram responded that his favorite thing was his “friends—they understand me and when I am tired, they still play with me.”

“YOU ARE NOT ALONE”

Dr. Christopher Austin, Director of the NIH’s National Center for Advancing Translational Sciences (NCATS), and Former Chair of the International Rare Diseases Research Consortium, then closed the day by telling everyone that “You are not alone; we are all related to each other.”

Earlier, he had repeated a quote that “Hope pertains only to those who take action, and that with no action, there is no hope.”

He encouraged everyone to continue to struggle, to fight, and to act so as to spur progress on rare diseases and to increase recognition of these diseases in the broader community.

And he wished everyone safe travels home.

STORIES EVERYWHERE

The stories of sadness, struggle, fortitude, courage, hope, and love were everywhere you looked or turned at this extraordinary gathering. More than anything, this was a story of the power and drive and love of parents fighting with everything they have to help their children, and the children of others. There is perhaps nothing more powerful in all of medicine than a parent struggling to help his or her child.

Here are just a few of the moving stories that I ran into as I walked around.

APPENDIX CARCINOMA & AUDREY HEPBURN

As I entered the NIH Hall at about 7.30 am, the first person I bumped into was 21-year-old Lauren Smith (http://tinypic.com/r/4sii39/9), who could not have looked healthier and was setting up a booth for the Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation (http://www.acpmp.org). I had recently heard about a highly curious possible connection between the appendix and Parkinson’s disease, but I had never heard of appendix carcinoma. Please go to the ACPMP web site (http://www.acpmp.org) to learn more about this rare disease and its various forms. Lauren told me that famous movie star Audrey Hepburn had died of appendix carcinoma at age 63, and that ESPN sportscaster and anchor Stuart Scott had also died of the disease at the age of 49.

Lauren, who is now Developmental & Communications Manager for the ACPMP Research Foundation, is a 2018 graduate of Merrimack College in Massachusetts where she received her BA in communication studies. She gained professional work experience through internships at a family and divorce law office and at Easter Seals New Hampshire. Lauren was diagnosed with low-grade mucinous neoplasm of the appendix in May of 2017. She will continue to be scanned annually. Having received her diagnosis early and at a young age, Lauren feels lucky and wants to continue to educate, raise funds, and promote awareness towards ACPMP for those who are still fighting or who may have courageously lost their battle to this rare disease. Lauren currently resides in Bedford, New Hampshire.

DYSTONIA 16 (DYT16)

During the lunch break, I noticed a poor young man who was being wheeled around in a wheel chair and was accompanied by his mother and also an aide. Hesitantly, I approached them to learn more about why they had come to RDD. It turned out that the young 21-year-old man’s name is Robert and he has the extremely rare disease known as dystonia 16 (DYT16) (https://rarediseases.info.nih.gov/diseases/10539/dyt-prkra). This disease is so rare that Robert may be the only person in the United States known to have it.

Robert’s mother, Jeneva Burroughs Stone, a professional writer, said that Robert’s disease had only recently been correctly diagnosed by Ada Hamosh (https://www.hopkinsmedicine.org/profiles/results/directory/profile/00028...), MD, MPH, Professor of Pediatrics at Johns Hopkins, and the precise molecular defects had been confirmed by exome sequencing carried out by Dr. Jimmy Lin, MD, PhD (https://drjimmylin.com/), now Chief Science Officer at Natera.

According to the NIH NCATS GARD web site (https://ncats.nih.gov/gard), dystonia 16 (DYT16) is a very rare and newly discovered movement disorder that is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism. It has been described in eight patients from three Brazilian families and one German family to date, the site said, and now Robert can be added to that list.

The disease presents in infancy to late childhood with one of two possible phenotypes: either generalized dystonia or dystonia-parkinsonism not responsive to L-dopa. Dystonia usually starts in one limb, becomes generalized and mainly affects the trunk, neck and oromandibular muscles. Motor and speech developmental delays were also reported. The phenotypic spectrum of this disease is still being determined. Pharmacological therapy is ineffective.

DYT16 is caused by mutations in the protein kinase, interferon-inducible double-stranded RNA dependent activator (PRKRA) gene, located on chromosome 2q31.2. DYT16 is inherited in an autosomal recessive manner.

Robert’s mother Jeneva said that Dr. Lin’s sequencing showed that one of her two chromosome 2’s bore a mutation in the PRKRA gene, but her husband’s two chromosome 2’s were normal. Apparently, her husband’s sperm had undergone a mutation in the PRKRA gene and that mutation had been passed on to her son Robert, along with his mother’s mutated chromosome 2. Thus, Robert has mutations in the PRKRA gene on both of his chromosome 2’s and therefore inherited the exceedingly rare autosomal recessive disease.

Jeneva, who has written the draft of a book on her experience with Robert and his struggles with dystonia 16, noted that the Parkinson’s medication Sinemet has been somewhat helpful to Robert.

Jeneva’s email is jenevastone@gmail.com; her author website is http://www.jenevastone.com, and her blog (“Busily Seeking Redux”) is at http://www.jenevastone.blogspot.com.

HUNTINGTON'S DISEASE & MIS-DIAGNOSED TICK-BORNE INFECTION

I was walking out of the NIH RDD event at the end of the day with my good friend Jonathan Monkemeyer, who had first alerted me to the NIH RDD event, which he had attended in the past, and who has his own heart-rending story of personal tragedy with a rare disease.

Jonathan had been a very high-end electrical engineer working in the GE space program, but then his wife was diagnosed with Huntington’s disease. Jonathan dropped everything to care for his wife in every way he could and also to learn as much as he could about the rare disease and how he might try to help his struggling wife.

Sadly though, despite his herculean efforts, his wife died—-but Jonathan has continued his efforts to understand and possibly help those with Huntington’s disease. Although I myself have an advanced degree in immunology from Duke, I think Jonathan has a far better grasp of molecular biology now than I do. Plus, because he looks at everything from his different engineering perspective, he seems to bring unique and compelling interpretations to what he studies.

About five years ago, Jonathan had his own direct experience with a relatively unusual disease when he came down with a tick-borne infection that was not the typical one, but a rarer one (anaplasmosis). This infection was initially misdiagnosed and not properly treated until Jonathan had lost his kidney function.

So, for the last five years, as the result of the incorrect diagnosis of a readily treatable infection, Jonathan has been on every-other-day kidney dialysis as he waits on the kidney transplant list. And he is just in his early 50’s. And yet, he remains upbeat and continues to use all of his still considerable energy to try to help others.

MOTHER WHOSE YOUNG ASPLENIC SON DIED FROM ACUTE BACTERIAL INFECTION

As Jonathan and I were walking out from the NIH RDD to head back to the hotel room we were sharing, we passed a woman standing by the path outside the NIH hall and looking at a map. We stopped to talk to her, and, sure enough, it was yet another story—perhaps one of the saddest of all that I had heard this day.

The woman, Allison Bones, had come to the meeting from her home in Phoenix, Arizona, because of her recent tragic experience of losing her four-year-old son Travis to an acute bacterial infection that took his life virtually overnight. It turned out that, although no one had known it, Travis had been born without a spleen and thus was highly vulnerable to infections.

As Dr. Austin suggested, despite her grievous loss, Allison has chosen to act and she has established an organization (TEAM 4 Travis) (Together Ending Asplenic Mortality) (http://www.team4travis.org), of which she is President. Allison may be contacted at allison@team4travis.com, 623-693-3317, PO Box 361, Litchfield Park, Arizona 85340. To add to Allison’s incalculable tragedy, shortly before Travis’s death, she also lost her husband to colorectal cancer.

TRAGEDY & HOPE

There is surely great tragedy amongst rare diseases, but there is also great hope. But as Dr. Austin said, “Hope only pertains if there is action.” So, all of us, healthy or sick, must take action to help those in need--and always remember, as we move along an often tough road, that “You are not alone, we are all together.”

--by Michael D. O’Neill, MA, Editor & Publisher, BioQuick Online News, logophile2000@yahoo.com, 914-374-1277

[Huntington's Disease News article]

Nine-year-old Amber, who has the very rare genetic disease giant axonal neuropathy (GAN), and her family, see, for the first time, the new Beyond the Diagnosis portrait of Amber at signature event of Rare Disease Day at NIH on February 28, 2019. Patricia Elaine Weltin, Founder & CEO of Beyond the Diagnosis is shown at left. Portrait was painted by Beyond the Diagnosis volunteer artist Jota Leal.

Dr. Francis Collins, NIH Director, at right in picture below, tweeted the following after the unveiling of Amber's beautiful portrait: "I was honored to unveil Amber’s portrait with Patricia Weltin @BeyondtheDx at last week’s #RareDiseaseDay2019 #RDDNIH. Amber has Giant Axonal Neuropathy. Her stunning portrait was donated by an artist raising awareness of rare diseases through art. #NIH"