The Grace Wilsey Foundation has put together a fantastic video!
Rare is not an excuse:
Please share!
Rare is not an excuse:
Please share!
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NGLY1 in The New Yorker!
Open science and social media were key in the discovery and growth of the NGLY1 rare disease community. Article by Seth Mnookin.
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NGLY1 Deficiency Research
In June 2012, the Freeze Lab pioneered research into the clinical treatment of the rare disorder, N-glycanase deficiency.
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NGLY1 Families Connect
On February 28, 2014, researchers and 5 NGLY1 families from across the world met for the first ever symposium on N-glycanase deficiency.
Monday, November 24, 2014
Sunday, November 9, 2014
2nd World Conference on Congenital Disorders of Glycosylation for Families and Professionals
Lyon, FRANCE
August 29 - 30, 2015
The CDG Community is planning “The 2nd World Conference on Congenital Disorders of Glycosylation for Families and Professionals: a challenging story of sugar trees”, early in advance. Due to relevant operational reasons, getting a detailed tentative agenda is of high importance.
This cutting-edge family and medical event will be held in 29 and 30 August 2015, in Lyon (France). It should be noted that this congress is organized in parallel with the Annual Symposium SSIEM that will be held in Lyon, 1-4 September 2015 (France).
“The 2nd World Conference on Congenital Disorders of Glycosylation for Families and Professionals: a challenging story of sugar trees” is expected to draw more than 250 attendees consisted of families and the main CDG professional Key Opinion Leaders coming from all countries. Speaker presentations will cover a diverse range of themes previously voted on.
View the outstanding speaker lineup from the 2013 event here:
Saturday, November 8, 2014
NGLY1 Deficiency Video
The Grace Wilsey Foundation has created an informational video to answer the question: "What is NGLY1 Deficiency?"
Please share with all those whom might be interested:
Please share with all those whom might be interested:
Saturday, October 25, 2014
Dr. David Goldstein to direct Institute for Genomic Medicine at Columbia University
NEW YORK (September 23, 2014) — David Goldstein, PhD, will join Columbia University as professor of genetics and development in the College of Physicians and Surgeons and director of a new Institute for Genomic Medicine in partnership with NewYork-Presbyterian, effective January 1, 2015. Dr. Goldstein will be responsible for building a program that comprehensively integrates genetics and genomics into research, patient care, and education at Columbia University Medical Center (CUMC) and NewYork-Presbyterian and that develops programs to prepare students for careers in the expanding field of genomic and personalized medicine.
David Goldstein, PhD, will join Columbia University as professor of genetics and development and director of a new Institute of Genomic Medicine. (Image Credit: Duke Photography)
Dr. Goldstein’s role includes serving as an adviser to Columbia University President Lee C. Bollinger and Executive Vice President for Health and Biomedical Sciences Lee Goldman, MD, on the genetic and genomic components of Columbia’s university-wide initiative in precision or “personalized” medicine, which was announced in February.
“Having a pioneering researcher like David Goldstein join us marks a crucial next step in our initiative to be at the forefront of genomics, data science, and the core science and engineering disciplines essential to this emerging field of truly humanistic medicine,” said President Bollinger. “The potential for progress in this broad subject encompasses not only new cures for disease, but also virtually every part of the University, including areas that explore fundamental issues of human self-understanding, as well as the legal, policy, and economic implications of revolutionary changes in knowledge and practice.”
Dr. Goldstein’s research has focused on identifying the relationship between human genetic variations and diseases such as epilepsy, hepatitis C, and schizophrenia, as well as the response of these diseases to pharmacologic treatments. In addition to his leadership of the Institute for Genomic Medicine at CUMC, he will have a faculty appointment at the New York Genome Center, as well as one in neurology at Columbia’s College of Physicians and Surgeons.
“David Goldstein has shown himself to be both an innovative scientist and a visionary leader in genetic, genomic, and personalized medicine,” said Dr. Goldman, who is also the Harold and Margaret Hatch Professor of the University and dean of the Faculties of Health Sciences and Medicine at CUMC. “Working with our partners across Columbia and at New York-Presbyterian, Dr. Goldstein will help us establish a fully integrated genetics and genomics research environment to maximize the scientific possibilities and apply them to the frontiers of patient care and public health.”
“Personalized medicine and targeted therapies represent the future of patient-centered health care,” said Steven J. Corwin, MD, CEO, NewYork-Presbyterian. “Dr. Goldstein’s expertise in genetics will help us not only to tailor individualized treatments for patients, but also to identify diseases before they develop. His work will have a transformative impact on patient care at NewYork-Presbyterian.”
Dr. Goldstein comes to Columbia from Duke University, where he has been director of the Center for Human Genome Variation and the Richard and Pat Johnson Distinguished University Professor, with appointments in the departments of molecular genetics & microbiology and biology. He joined Duke in 2005 after six years at University College London, which named him Honorary Professor in 2007. He received his PhD in biological sciences from Stanford University in 1994.
“The vision of Columbia University and NYP to create a truly integrated environment for research, clinical application, and student instruction is exactly the right vision,” said Dr. Goldstein. “Human genomics is creating breathtaking new opportunities to better understand the biology of disease and to provide more effective and more accurately targeted therapies. Capitalizing on these opportunities and ensuring that clinical applications adhere to the highest-possible scientific standards requires close collaborations among researchers, the clinical community, and patients and their families. I am thrilled to be joining Columbia University at this pivotal time in my field, and I am honored to participate in Columbia’s university-wide initiative in precision medicine.”
Dr. Goldstein was elected a fellow of the American Association for the Advancement of Science in 2013 and received one of the first seven nationally awarded Royal Society/Wolfson research merit awards in the United Kingdom for his work in human population genetics. Also in 2013, Dr. Goldstein chaired the Gordon Research Conference in Human Genetics. He serves on the Advisory Council at NIH’s National Institute of Neurological Disorders and Stroke.
The task force President Bollinger announced in February is co-chaired by Dr. Goldman and Columbia Provost John Coatsworth, PhD.
About:
Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.NewYork-Presbyterian Hospital/Columbia University Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and its academic partner, Columbia University College of Physicians and Surgeons. NewYork-Presbyterian/Columbia provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, research, education and community service. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian Hospital/Weill Cornell Medical Center, NewYork-Presbyterian/Morgan Stanley Children’s Hospital, NewYork-Presbyterian Hospital/Westchester Division, NewYork-Presbyterian/The Allen Hospital and NewYork-Presbyterian/Lower Manhattan Hospital. The hospital is also closely affiliated with NewYork-Presbyterian/Lawrence Hospital in Bronxville. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area, according to U.S. News & World Report, and consistently named to the magazine’s Honor Roll of best hospitals in the nation. For more information, visit www.nyp.org.
Monday, August 25, 2014
NGLY1 Profile: Grace, age 4
Parents: Kristen and Matt
Sibling(s): none
History
Grace was delivered via emergency Caesarean section at Lucile Packard Children’s Hospital at Stanford in 2009. The doctors hit the “crash” button because of decreasing fetal heart rate. Grace's Apgars were 4 at 1 minute and 8 at 5 minutes. She spent the first 2 nights in our room at the hospital, but she was extremely lethargic, was not eating, or going to the bathroom. Her eyes looked hazy and quite gray. Her pediatrician ran a series of blood tests and Grace's CRP (a non-specific marker for stress such as an infection) was extremely elevated (~12). The doctors quickly moved Grace to the NICU for a little over 2 weeks.
The doctors ran all kinds of tests on her from a spinal tap to a brain ultrasound to an EKG to multiple stomach x-rays. They never could tell if she had a viral or bacterial infection, but they were fairly sure it was one or the other. Consequently they gave her 2 full weeks of antibiotics and a few days of antivirals. Every 24 to 48 hours Grace improved slightly. It seemed the drugs were working. Toward the end of her 2-week stay, her liver enzymes (known as LFTs for short) were shown to be elevated and her platelet count was dangerously low. The doctors thought this was most likely a residual effect of the infection and sent us home to be monitored as an outpatient (we were told there was nothing more they could do in the intensive care unit). Shortly before Thanksgiving 2009, the liver enzymes normalized and an abdominal ultrasound showed the liver working normally. We felt like we dodged a bullet and we decided to retest at 5 to 6 months of age after working closely with Grace's gastroenterologist at Stanford.
Unfortunately the tests at 5 months showed elevated AST and ALT (GGT was normal). On top of the elevated LFTs, Grace was falling behind developmentally. This is where we mobilized in a big way because clearly this was not a reaction to an infection and was not isolated to GI. This was something very serious and something genetic.
We assembled the best and brightest clinical minds in several disciplines at many world-class centers. We made 3 trips to Columbia, 2 trips to CHOP, 2 trips to NIH, 2 trips to Baylor College of Medicine / Texas Children’s Hospital, 1 trip to University of Colorado, Boulder, 1 trip to John Hopkins, and countless trips to Stanford and UCSF. From the age of 6 months to 3 and ½ years old, we pursued a primary mitochondrial disease.
Whole Genome Breakthrough
After exhausting all of our testing options, two centers (Stanford and Baylor) independently performed whole genome sequencing (WGS). We wanted to see if both came up with the same conclusion independently. Stanford and Baylor came back with the exact same leading gene candidate (SUPV3L1). This gene fit Grace’s phenotype and the theory that Grace’s condition was mitochondrial. We spent nearly 1 year investigating this gene under the close supervision of Dr. Greg Enns at Stanford and Dr. Vamsi Mootha at Harvard / Broad. Unfortunately the functional assays did not prove anything.
In addition to SUPV3L1, Stanford and Baylor flagged several other “candidates” (genes that looked suspicious). We explored several of these, but not all. In February 2013, Kristen, Grace, and I flew back down to Houston for 4 days. Under the guidance of Dr. Huda Zoghbi, we met with over 15 doctors in 3 days. Two of the doctors we met with were Richard Gibbs and Matthew Bainbridge. We asked them to re-run our data. Within a few days of meeting, Matthew emailed asking if Grace produced tears. We had noted to several specialists that Grace did not produce streaming tears when sad or hurt, but this clue didn’t help us over the previous years. Richard and Matthew had flagged one gene in particular (NGLY1). This gene was actually flagged by Stanford back in 2011, but it was a mystery gene. At the time, no databases or medical literature showed one human being having a NGLY1 mutation. Unbeknownst to Stanford and us, the doctors at Duke had diagnosed Bertrand and were preparing to publish. Once they did publish, Richard and Matthew found it. The phenotypes, while not perfect matches, were close. The lack of tears while crying was a significant clue in piecing the puzzle together.
Current Health Condition
Grace is stable. While she has many challenges, she is amazingly happy and resilient. Despite spending a lot of time in hospitals and clinics, she is relatively healthy for a 4 year old NGLY1 patient. Colds affect her more than most kids (her body gets “floppy”), but she recovers quickly. Developmentally she is more like a 12 to 18 month old. She can sit-up, pull-up to stand, “cruise” along furniture, and walk for short distance after pulling up to stand. She cannot talk. She has a few sounds and word approximations. She cannot point and has no pincer grasp (index finger + thumb). Her disease affects her central nervous system (CNS), liver, and muscle predominantly. She has microcephaly (small head), difficulty gaining and maintaining weight, alacrima (dry eyes), sleep apnea, and strabismus (eyes wander). The systems we have to keep close tabs of are liver, eyes, and lungs. The latter has showed some signs of aspiration, which is quite dangerous (pneumonia can be lethal in young kids with chronic / rare illness). Grace loves Elmo, books, music (Katy Perry, Taylor Swift, & Super Simple Songs), Super Grover 2.0, swimming, and horses.
Monday, August 18, 2014
NGLY1 Profile: Mason, age 5
Patient: Mason, age 5
Parents: Sara and Mark
Sibling(s): none
Mason is five years old and was born at 34 weeks via emergency C-section because of bradycardia episodes, he was measuring small and my fluid level was dangerously low. He was a relatively 'normal' preemie, staying in the NICU for 24 days, his main issues were jaundice, finally passing the merconium, and learning to eat and hold his temperature. He was on oxygen for only the first 24 hours and progressed somewhat normally in the NICU. He had a Hirschprung's test done because it took him longer than 7 days to pass the merconium; but that test came back negative.
Mason came home weighing 5lbs, he cried almost all the time when he was awake, wouldn't sleep for longer than 45 mins at a time and projective vomited almost everything he ate. He was never very good at latching on, so I pumped for 3 months and bottle fed him, until putting him on specialty formula, all of which didn't help. He was tested for allergies and other than having a sensitive to dairy, there was nothing.
Mason was always a heavy breather, in fact we would joke that he was like Darth Vader. He went in for an MRI after the neurology visit and they refused to put him under because of the stridor. He saw an ENT who thought he just needed to grow a little bigger and hopefully his airway became strong; they attributed the stridor to the reflux. He finally got an MRI, and overall his brain was 'smaller' than normal, but there was nothing significantly glaring - little did I know this meant absolutely nothing!
At about 13 months, he was hospitalized for severe breathing issues; he sounded like he was breathing from a straw. It was at this 5 day stay where they did the muscle biopsy, found that he has only one kidney, and still attributed the stridor to severe reflux; they put him on feeding through an NG tube and his breathing seemed to get better so they sent us home. (Not to mention that they stuck him one million times trying to get an IV so they could fly him, then another million times to do tons of tests...he's one of the toughest little guys ever). They sent us home on a steroid, once he was off the steroid, the breathing got worse, so he was sent back to the hospital to get the Nissen Fundoplication surgery. The hope was that if he physically couldn't throw up, his airway wouldn't be burned by the acid and then his airway wouldn't be inflamed and breathing would improve. During the Nissen, they did a livery biopsy to check to Mito disease. It was after the muscle and liver they told us he had mito - I never realized that when they classified him with this it was because he had too much mitochondria!
Unfortunately, after another round of steroids and being sent home, his breathing was still awful, so they told us he would need to be trached. One month later, he had his trach surgery. We were told he would be kept asleep for a week so that he could heal and wouldn't pull at his trach - they kept him under for only a few hours after surgery and when he woke it was one of the most heartbreaking moments a mother could have, as I'm sure you can relate. For the first two months, we couldn't leave the floor, it was like the best moment of my life when we were allowed to walk around the entire hospital. In total, we were in the hospital from August to December. As difficult as it has been to get used to the trach, it has allowed him freedoms he never before had now that he can breathe.
Over a year ago we noticed his head drops and eye rolls getting significantly worse, mind you we took him off the Keppra, but thought we were ok because we never could see the seizure. Within 10 mins of his EEG, the on-call neurologist was called and Mason is literally having thousands of seizures a day; most go without anyone noticing, but they definitely get in the way of his development.
Mason cannot walk, he cannot talk, there is a 'light' on, he recognizes people and places, knows what he wants and can communicate without words and he smiles like it's Christmas watching Mickey Mouse. He can crawl and sit on his own and pull to stand. Overall he is the most incredibly loving and strong little boy.
Thursday, July 24, 2014
US Congress hears about NGLY1
On Tuesday, July 22, 2014, at 3:00 p.m. in 2322 Rayburn House Office Building, the Subcommittee on Health held a hearing entitled “21st Century Cures: Examining Barriers to Ongoing Evidence Development and Communication.” This hearing focused on issues surrounding continued evidence development and communication of information regarding treatments and cures in the real world setting.
In her opening statement, Rep. Diana DeGette (Colorado) used NGLY1 as an illustration, and goes on to ask, "What can we do to harness this [patient involvement and technology] in a much more systemic way, so that these types of communications can happen effortlessly both in the United States and with our colleagues around the world?"
Learning about the benefits and risks of a drug or device does not end when the Food and Drug Administration approves, licenses, or clears the product for use in certain patients based on the evidence presented during the premarket review process. In many ways, the process is just beginning.
Different uses for drugs and devices are being discovered constantly, many times for treatment of new conditions and diseases or for populations of patients other than for which they were initially approved. Treatment in the real world setting also provides the opportunity to learn more about both the benefits and risk profile of a drug and device for its indicated use, as well as other uses.
Learning and data sharing regarding safety and efficacy are happening through a multitude of platforms around the globe. Dialogue regarding this enhanced learning--whether through the Internet, social networks, or other platforms--should be facilitated among doctors, patients, researchers, and scientists because the free flow of data, research, and results related to what a therapy or combination of therapies does or does not do well and in what types of patients could help advance the discovery, development and delivery cycle.
Wednesday, July 23, 2014
Boston Public Radio covers NGLY1
The segment on NGLY1 starts at 1:36:39.
Seth Mnookin, a professor in the MIT graduate program in science writing, talked about his new piece in The New Yorker titled "One of a kind: What do you do if your child has a condition that is new to science?"
Monday, July 21, 2014
Benefit for Jordan & Jessie
The following is a fundraiser to improve the quality of life for one of our beautiful NGLY1 families by helping them purchase a handicap accessible van capable of transporting both of their daughters.
If anyone is interested in simply donating directly to this family, please let us know. Thank you!
Everyday life for The Stinchcomb's is tough. Both girls who suffer from NGLY1 do not speak, they can not walk, they wear diapers, drink formula, use wheelchairs, and need constant attention. Tony and Pam provide all of this to their girls WITHOUT ANY OUTSIDE HELP. They see that the girls' needs are met to the best of their ability. Traveling, even to the grocery store, is nearly impossible, even with their Suburban. The one single thing that could change the quality of life for this family would be handicap accessible transportation. That is our goal with this fundraiser. Helping them achieve mobility so their family can function more like an every day family!
This family is near and dear to our hearts so I wanted to do something special for them. You can help by placing an order online anytime between now and August 15th and I will donate 25% to the Stinchcomb Family! This is a great opportunity to help this sweet family, and also get a gift for someone special (or yourself)! Don't forget Christmas, Birthdays, Teachers and special occasions!
Order at:
http://www.heatherm.origamiowl.com /parties/ StinchcombFundraiser405289/ collections.ashx
Saturday, July 19, 2014
"Integrating Glycoscience"
This upcoming November 2014 at the annual joint meeting for the Society of Glycobiology and the Japanese Society for Carbohydrate Research, there will be an entire session dedicated to NGLY1!
The theme for the conference is "Integrating Glycoscience From Biology and Chemistry to Medicine".
NGLY1 session presenters will include researchers Tadashi Suzuki, Hudson Freeze, Hamed Jafar-Nejad, as well as two NGLY1 parents! The Super Matts: Matthew Might and Matt Wilsey.
The NGLY1 session starts at 2:45pm on Tuesday, November 18th. These talks are sure to be thought-provoking and inspiring.
If you'll be in Honolulu, Hawaii, don't miss it!
Friday, July 18, 2014
NGLY1.org Facebook Launch
In 2012, we launched NGLY1.org as a resource to clinicians, a means of finding new N-glycanase (NGLY1) deficiency patients, and a way to support their families.
Yesterday, thanks to the rapidly growing NGLY1 community, we launched the NGLY1.org page on Facebook to facilitate NGLY1 family-researcher interaction and provide support.
We invite everyone to join! The page will be a public one, but we reserve the right to make it private if necessary in the future.
We will continue to promote N-glycanase deficiency, so patient families will be able to find the NGLY1 community and receive the same valuable support.
Tuesday, July 15, 2014
NGLY1 in "The New Yorker"
It is an honor to have an ultra-rare disease brought to public attention with such compelling and thorough reporting.
On behalf of all NGLY1 patients and their families, including those yet undiagnosed: Thank you, Seth!
You can read the full article HERE.
Monday, July 14, 2014
What is a "Natural History of Disease"?
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| The NIH Campus in Bethesda, Maryland, USA. |
The natural history of disease refers to a description of the uninterrupted progression of a disease in an individual until recovery or death.
Knowledge of the natural history of disease ranks alongside causal understanding in importance for disease prevention and control.
Natural history studies and registries also play a critical role in the drug discovery and development process.
Standardized natural history registries, tied to tissue banking, facilitate the generation of research leads, and accelerate studies examining associations between phenotype (disease-related physical and mental characteristics) and genotype.
Patient registries represent one of the best resources to collect prevalence, demographic, natural history, and comparative effectiveness data on rare diseases.
Currently, very few rare disease patient registries exist and where they do, they are often limited in their usefulness.
The NIH, FDA, and NORD are currently in the process of building a rare disease patient registry program to ensure rare disease patients have adequate natural history information in order to spur drug discovery and development.
Sunday, July 13, 2014
NIH NGLY1 Study Experience
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| Bertrand with NIH study coordinators, Lynne Wolfe and Christina Lam. |
The following links provide an overview of the study experience from the patient/family perspective:
Tuesday, July 1, 2014
NIH names new clinical sites in Undiagnosed Diseases Network
David Goldstein and Vandana Shashi, who headed up the team at Duke that discovered N-glycanase deficiency, will also be heading up one of the sites for the Undiagnosed Diseases Network (UDN). The UDN is a large step forward for undiagnosed patients everywhere. We are hopeful that many families will soon be getting answers thanks to dedicated researchers like Drs. Goldstein and Shashi.
Bethesda, Md., Tues., July 1, 2014 - The National Institutes of Health has awarded grants to six medical centers around the country to select from the most difficult-to-solve medical cases and together develop effective approaches to diagnose them. The clinical sites will conduct clinical evaluation and scientific investigation in cases that involve patients with prolonged undiagnosed conditions. Each clinical site will contribute local medical expertise to the NIH Undiagnosed Diseases Network (UDN). The network includes and is modeled after an NIH pilot program that has enrolled people with intractable medical conditions from nearly every state, the District of Columbia and seven foreign countries. The network builds on a program at the NIH Clinical Center in Bethesda, Md., that for the past six years has evaluated hundreds of patients and provided many diagnoses, often using genomic approaches, for rare conditions.
"Newly developed methods for genome sequencing now provide us amazingly powerful approaches for deciphering the causes of rare undiagnosed conditions," said Eric D. Green, M.D., Ph.D., director of the National Human Genome Research Institute. "Along with robust clinical evaluations, genomics will play a central role in the UDN's mission." Dr. Green and Story Landis, Ph.D., director of the National Institute of Neurological Diseases and Stroke, co-chair the UDN working group.
Undiagnosed diseases are conditions that even skilled physicians cannot diagnose despite extensive clinical investigation. They may not be recognized by doctors because they are rarely seen, are previously undescribed, or are rare forms of more common diseases.
The NIH Common Fund awarded four-year grants of approximately $7.2 million (pending available funds) to each of the six medical centers around the country. James M. Anderson, M.D., Ph.D., director of the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), announced in an NIH telebriefing that the six newly awarded sites join a clinical site already established at NIH in pursuing cutting-edge diagnoses. In addition, this past December, NIH selected Harvard Medical School as the UDN Coordinating Center for the multi-institution network. "The NIH Undiagnosed Diseases Network has the potential to transform medicine and serve as a catalyst for new discoveries," said Dr. Anderson. "It is an ideal NIH Common Fund program-the only one focused on diagnoses of rare disorders."
The following institutions were awarded grants to establish UDN clinical sites:
- Baylor College of Medicine, Houston; Principal Investigator: Brendan H.L. Lee, M.D., Ph.D.
- Boston Children's Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital, Boston; Principal Investigator: Joseph Loscalzo, M.D., Ph.D.
- Duke University, Durham, North Carolina; Principal Investigators: David B. Goldstein, Ph.D, and Vandana Shashi, M.D.
- Stanford University, Stanford, California; Principal Investigators: Euan A. Ashley, M.D., D.Phil., Jonathan Bernstein, M.D., Ph.D., and Paul Graham Fisher, M.D.
- University of California, Los Angeles; Principal Investigators: Katrina M. Dipple, M.D., Ph.D., Stanley Nelson, M.D., Eric J. Vilain, M.D., Ph.D., and Christina Palmer, C.G.C., Ph.D.
"This type of program can invigorate a medical center anywhere in the country and in the world," said William A. Gahl, M.D., Ph.D., clinical director at the National Human Genome Research Institute (NHGRI), director of the NIH-based Undiagnosed Diseases Program (UDP) and co-coordinator of the UDN working group. "Often, patients have a lot of physical complaints and no objective diagnoses. Our goal is to use the latest tools to make a diagnosis that spans the clinical, pathological and biochemical spectrum to uncover the basic genetic defect." Since 2008, the UDP has explored this fascinating area of medical research and acquired practical insights in the process of enrolling approximately 600 undiagnosed children and adults in its clinical protocols. The multidisciplinary clinical and research team diagnosed approximately 100 patients (20-25 percent of those evaluated), discovered two unknown diseases and identified 15 genes not previously associated with any other human disease. A combination of genomic and clinical analyses contributed to the diagnoses.
- Vanderbilt University Medical Center, Nashville; Principal Investigators: John H. Newman, M.D., and John A. Phillips, III, M.D.
By including an additional six clinical sites, the NIH UDN will both draw upon the unique expertise of new clinical research groups and cultivate opportunities for collaboration among a larger group of expert laboratory and clinical investigators. Physicians within the network will collect and share high-quality clinical and laboratory data, including genomic information, clinical observations and documentation of environmental exposures. They also will benefit from common protocols designed to improve the level of diagnosis and care for patients with undiagnosed diseases.
"The UDN will look at diseases across all clinical specialties using new tools and methods of analysis for the identification of new diseases," said Anastasia L. Wise, Ph.D., a program director in NHGRI's Division of Genomic Medicine and co-coordinator of the UDN working group that oversees the development and implementation of the UDN. "The network will facilitate collaboration and shared use of genomic tools among the sites." Based on the NIH UDP experience, the UDN Coordinating Center at Harvard Medical School has begun paving the way for the new UDN clinical sites to begin accepting patients. Among the coordinating efforts are the preparation of draft protocols and operating guidelines, and the definition of an initial framework of common practices across the network. The network will share systems for data collection and develop common approaches to patient selection, evaluation and diagnosis.
Each new clinical site may have variations in handling health insurance coverage for clinical testing and care. However, no patient will be turned away from participation in the UDN based on lack of health insurance coverage.
"We believe that there is a substantial unmet demand for the diagnoses of conditions that have perplexed skillful physicians," said Isaac Kohane, M.D., Ph.D., professor of pediatrics at Harvard Medical School and Boston Children's Hospital and principal investigator of the Coordinating Center. "We want to address inquiries from physicians and patients throughout the country who require these services and, in doing so, create a 21st century model for diagnosis and treatment in this genomic and information-intensive era."
UDN investigators will share genomic data from UDN patients with the research community through multiple public repositories. Network-wide data sharing will observe standards of patient privacy, confidentiality and management of health information.
The network will start up and test its operating procedures during its first year. It will progressively expand recruitment of patients so that by the summer of 2017, the rate of admissions at each new clinical site will be about 50 patients per year. For a period this summer, referrals from clinicians on behalf of undiagnosed patients may continue to be made through the existing NIH application pipeline.
Instructions on applying to the UDN on behalf of a patient can be found at rarediseases.info.nih.gov/undiagnosed.
For more information about the UDN, including related funding announcements, visit http://commonfund.nih.gov/Diseases/index.
These UDN clinical site awards are supported by NIH grants 1-U01HG007672-01, 1-U01HG007674-01, 1-U01HG007709-01, 1-U01HG007690-01, 1-U01HG007708-01, 1-U01HG007703-01.
NHGRI is one of the 27 institutes and centers at the National Institutes of Health. The NHGRI Extramural Research Program supports grants for research and training and career development at sites nationwide. Additional information about NHGRI can be found at www.genome.gov.
The NIH Common Fund encourages collaboration and supports a series of exceptionally high-impact, trans-NIH programs. Common Fund programs are designed to pursue major opportunities and gaps in biomedical research that no single NIH Institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Common Fund can be found athttp://commonfund.nih.gov.
National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 institutes and centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
Sunday, June 29, 2014
Parental Might
Friday, June 13, 2014
Grace Wilsey Foundation
The Wilsey family just launched the Grace Wilsey Foundation to fund NGLY1 research and, more broadly, change the way rare diseases are researched. Kuddos, Matt and Kristen!
Thursday, June 12, 2014
NGLY1 Profile: Kaylee, age 4
Patient: Kaylee, age 4
Parents: Kelsey and Daniel
Sibling(s): Justin, age 2
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Prenatal:
At about 20 weeks pregnant my OB discovered that Kaylee only had a 2 vessel chord and was a lot smaller that she should be, at the time the chord was thought to be the only reason. We monitered her very closely from that point on. At about 28 weeks I started having twice a week non stress tests (NST's) and weekly ultrasounds. Almost every time I went in for her NST's she showed little or no movement even after they would use the buzzer to try to irritate her, which resulted in ultrasounds to make sure she was ok, she always checked out in these ultrasounds. At 33 weeks she had a large ultrasound at a specialty clinic to get exact measurements and a good estimate of her weight. She had a follow up ultrasound at 37 weeks which showed that she hadn't grown at all between the two. I went to my Dr. appointment directly after that ultrasound and they admitted and induced me that afternoon. After several hours of labor they noticed Kaylee's heart rate drop with each contraction and we had to do an unplanned c-section. She was born 4 lbs 2 oz and 18 in long. Due to her size she was admitted to the NICU and stayed for 8 days. Her lungs were fully developed and she appeared healthy, their only concern at that point was her ability to eat and maintain her own body heat due to her size. She was in an incubator for several of those days and spent 2 days under the billy lights for what they considered mild jaundice. She also had an NG tube placed to help her eat. By the time she was released at 9 days old she was eating on her on and cleared as healthy.
Diagnostic journey:
At about 10 months of age we started noticing that she was more that a little bit delayed. She was rolling over but not scooting or crawling at all. She also had been very small her whole life, but it had not been concerning because she had been growing on her own consistent curve. At this point she had stopped growing and her pediatrician started showing a lot of concern. At 11 months of age we saw her first specialist, a GI Doctor. She had recommended an NG tube and continuing to a G-tube shortly after. We had to quit Kaylee's breastfeeding cold turkey and move her to formula so we could see exactly how much she was eating. After a few days of this we discovered that she was consistently taking only about 7 oz in an entire day, which is way too little!! At this point we transferred her care to our Seattle Children's hospital so that we could have it all done in one place, and they have fantastic financial aid. We quickly scheduled her NG placement at 11 months of age because of how little she had eaten and the had dropped for about 16 lbs to about 14lbs. Her weight showed immediate improvement from the NG tube. At the time she also had blood drawn and showed elevated liver functions and low white blood counts. About a year later we placed a G tube and she is still on this today.
Soon after seeing her GI Dr. we started seeing a biochemical geneticist and a variety of other Dr.'s. Her geneticist suspected she had a mitochondrial disorder. She was pretty quickly tested for several of the more common ones via blood tests, and had a brain MRI, muscle biopsy and liver biopsy all at one time when she was about 15-18months old (I don't remember her exact age). Her MRI and muscle biopsy were clear, but her liver biopsy showed some cirrhosis of the liver, and at the time they told us she might eventually need a liver transplant. Since then her liver functions have continued to stay about the same and they no longer believe a transplant is likely to become necessary. As well all of the blood tests we did over the next 1 1/2 years came back negative for all known mitochondrial disorders they could test for. We had discussed at about 3 years of age a whole exome sequencing test but they were having some problems requesting them and at this point her Dr. thought that anything we found out would be informational and have no treatment so we held off on the testing for a while. We did her test in April of 2013 and got her results in September (almost 4 years of age, 3 years after we began testing) which showed she had mutated NGLY1 genes which her doctor knew nothing about. He did some research and in December we were referred to Dr. Hudson Freeze and from there we were able to meet Cristina and several other families.
In the mean time off all the big tests we also did hearing tests which came back normal, an eye exam which showed that her sight was normal. We did swallow studies, liver ultrasounds, bone age X-rays, hip and spine X-rays and countless blood tests to continue to check her liver functions and white blood cell and platelet counts. Which were both low at some points but normalize at times. We discovered that her spleen is destroying her platelets, which we still are not sure why but believe it's because her spleen is working too hard because her liver isn't functioning properly, we have discussed the possibility of needing a stint to be placed to bipass her liver if her spleen continues to be enlarged and work too hard.
Symptoms:
Kaylee has had:
elevated liver functions
low white cell counts
low platelet counts
cirrhosis of the liver
enlarged spleen
very low production of tears
lack of muscle tone
Physical delays:
crawls (started at about 2 yrs of age)
pulls up to stand
takes some steps with the use of a gait trainer (walker)
Is just beginning to try to use an ipad for communication, she has no words
She has very poor fine motor skills, has difficulty with purposeful movements to complete a task
She also uses foot braces for very tight heal chords, significantly tighter in her left foot.
Wednesday, June 11, 2014
NGLY1 Profile: Tim, age 3
Patient: Tim*, age 3
Parents: C and A
Sibling(s): none
"Tim" was born in June 2011 by Cesarean section at 39 weeks after fetal distress was noted. He weighed only 2.3 kg at birth - intrauterine growth restriction (IUGR) had been noted at around 34 weeks of pregnancy and a biopsy of the placenta showed necrotic tissue. He had mild hyperbilirubinemia which did not require treatment, but otherwise his neonatal course was unremarkable and we were discharged on day three.
It was not long after that our journey began. Something seemed not right with Tim. He was crying inconsolably, not sleeping well, he moved different from other babies, he could not hold up his head very well (and he kept on nodding – we only realized much later that those nods were seizures! No doctor had picked it up). He was floppy and lying in a C-shape. He did not like to be touched or soothed. He did not like noisy environments or other people in general. He was fussy. Somehow he always managed to reach his milestones just in time in those first months and since he was feeding well, no doctor got concerned. They always sent us home with words of encouragement such as “all babies are bad sleepers” or “some boys tend to develop more slowly” but we just KNEW that something was not right!
At 6 months we took him to a neurologist and she immediately confirmed our worst fears. Our son had “brain damage” and no, there was nothing we could do but try to ease the symptoms and carry on with our lives. We were devastated! We got Tim admitted to a big university hospital in Germany and all sorts of tests were done. It was so scary and unreal. Many results came back slightly abnormal (one of them was for CDG which in the end happened to be a close match to NGLY1 deficiency), but it was all unspecific and we were discharged with no diagnosis and even more fear than before. We had:
- global developmental delay
- generalized poly-spike discharges in the EEG
- elevated blood lactate levels
- elevated LFTs
- delayed myelination in the MRI
Soon after, Tim’s seizures started to get worse (we are pretty sure they had been there before) we started a long journey of finding the right medication. This journey led Tim to another hospital stay of almost two months. He had myoclonic jerks of arms and legs and nodded with his head (atonic seizures). We kept close track of the frequency. What started out with 20 seizures a day went up to 200 while the doctors kept changing his meds again and again. Tim was miserable. He got worse from day to day. He could barely move anymore and stopped smiling. The doctors started telling us that “this was the nature of his progressive disease”. A second MRI showed his brain was shrinking. It was horrifying.
Somehow, for lack of a better idea, doctors declared him to be a suspected case of mitochondrial disease. As one doctor put it “this is the only label under which we can combine the EEG and the liver findings”. We were so frustrated with these doctors and the hospital in general!
After some months we took him out of the hospital and off the meds, but we still had no diagnosis and no idea where we were headed. We started to note involuntary movements and Tim kept on getting eye infections which resulted in corneal scarring – we first blamed the high-dose steroid therapy while actually these were fundamental symptoms of his disease. He could not close his eye lids during sleep. He was severely constipated. His sleep pattern was highly pathological with hardly any deep sleep and many arousals during the night. He was constantly tired, and so were we.
On the positive side, time showed that his regression during the hospital stay was not due to his progressive disease but due to the treatment. The longer Tim was out of the hospital the more he recovered. A new MRI in spring 2013 – although still showing abnormal results like the first one – showed that Tim’s brain had re-gained its volume. We started milder interventions for treating the epilepsy like the ketogenic diet and phased meds in and out very slowly and not as abruptly as in the hospital. Still, except for Lamictal more than a dozen medications showed no effect or only negative side-effects. Lamictal helped at least a little bit with his sleep and mood. Tim’s greatest motor achievement during that time was learning to belly crawl a few months before his second birthday.
In the summer of 2013, briefly before his second birthday, I did an internet search for “ketogenic diet check up protocols” and found Cristina’s blog. I saw pics of Bertrand and immediately started reading about his symptoms. He looked and sounded so much like Tim!!! So I sent the Mights an email and received a reply the same day. We were so excited! They too thought Tim was a close match and put us in touch with their doctors. We sent his skin cells and DNA to the States and bam…a few weeks later we had a diagnosis! Tim was the first child to be only tested for NGLY 1 deficiency (and not whole exome/genome sequencing) and the 10th child to receive the diagnosis. He is the only German child so far.
Having a diagnosis has changed everything. We are no longer alone, but are in this together with some of the most wonderful families imaginable. The exchange between the families has been tremendously helpful and I am sure will continue to be so as we are working on finding a cure. Also, based on Bertrand’s experience and because we had run out of other options we were able to convince our doctors to put Tim on Valproate for his seizures (they had not dared to do so earlier because of his suspected mitochondrial disease). It took a long while (almost 6 months and increase up to 600 mg/day), but he became seizure free. He has been seizure free for more than three months now (knock on wood). He is a changed child. He has learned to sit up, to come on his hands and knees, to feed himself, and to take supported steps during this time. He babbles the whole day, and is so much happier and calmer than before.
“Overcomingmovementdisorder.com” has changed our lives and we’ll be eternally grateful to Cristina and Matt. We want to encourage all parents to never give up the search for a diagnosis – even if there is no cure yet, it can make a huge difference in your child’s and your own quality of life!
* Name has been changed to protect privacy.
* Name has been changed to protect privacy.
Saturday, June 7, 2014
NIH CDG/NGLY1 Study - Now Recruiting!
Clinical and Basic Investigations into Known and Suspected Congenital Disorders of Glycosylation
This study is currently recruiting participants.
Summary | Eligibility | Citations | Contacts
Summary
Number
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14-HG-0071
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Sponsoring Institute
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National Human Genome Research Institute (NHGRI)
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Recruitment Detail
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Type: Participants currently recruited/enrolled
Gender: Male & Female Min Age: 1 Max Age: 80 |
Referral Letter Required
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No
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Population Exclusion(s)
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None
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Special Instructions
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Currently Not Provided
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Keywords
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Natural History;
Glycosylation; Genetic Disorders |
Recruitment Keyword(s)
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None
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Condition(s)
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Congenital Disorders of Glycosylation
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Investigational Drug(s)
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None
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Investigational Device(s)
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None
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Intervention(s)
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None
|
Supporting Site
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- Proteins, fats, and other molecules are the body s building blocks. Many of these molecules must have sugars, or chains of sugars, attached to work properly. People with congenital disorders of glycosylation (CDGs) cannot attach these sugars or sugar chains properly. A child or adult with a CDG can have symptoms in different parts of the body, including brain, nerves, muscles, liver, and immune system. Researchers want to learn more about these diseases to understand better what is causing the problems.
Objective:
- To learn more about CDGs.
Eligibility:
- People age 1 80 with CDG or suspected to have a CDG.
Design:
-CDG participants will stay in the hospital 3 5 days. They will have:
-Medical history and physical exam. They will answer questions about their CDG.
-Blood taken several times. Their skin will be numbed, then a needle will take blood from an arm vein.
-Samples taken of their skin, urine, and maybe stool and spinal fluid.
-Photos taken of their whole body. They can wear underwear and cover their eyes.
-Brain MRI. They will lie on a table that slides in and out of a metal cylinder. The scanner makes loud knocking noises so they can wear earplugs.
-Abdomen ultrasound. Sound waves take images of the body from the outside.
-Hand/wrist X-rays for young patients. They may have a full-body X-ray.
-DEXA bone density scan. Participants will lie on a table under a scanner.
-Echocardiogram and electrocardiogram for heart activity. Pads are stuck on the skin and the electrical activity of the heart is recorded.
-Tests of hearing, thinking, motor skills, and speech.
- Children participants may have tests done under sedation if it will benefit them directly.
- CDG participants may have other procedures during their visit. They may have follow-up visits every year.
Eligibility
INCLUSION/EXCLUSION CRITERIA:
Patients of any gender and ethnicity age 1-80 years with a suspected CDG based on biochemical tests or a confirmed CDG based on enzymatic or molecular tests will be eligible to enroll in this protocol. Patients will also be excluded if they cannot travel to the NIH due to their medical condition. Infants under age one year or under 10 kg of body weight are excluded because care is more readily provided to older infants at the Clinical Center.
Citations:
Contacts:
Principal Investigator
|
Referral Contact
|
For more information:
|
| Christina T. Lam, M.D. National Human Genome Research Institute (NHGRI) | Lynne A. Wolfe, C.R.N.P. National Human Genome Research Institute (NHGRI) BG 10-CRC RM 3-2551 10 CENTER DR BETHESDA MD 20814 (301) 443-8577 wolfela@mail.nih.gov | Patient Recruitment and Public Liaison Office Building 61 10 Cloister Court Bethesda, Maryland 20892-4754 Toll Free: 1-800-411-1222 TTY: 301-594-9774 (local),1-866-411-1010 (toll free) Fax: 301-480-9793 prpl@mail.cc.nih.gov |
