{"id":981,"date":"2016-02-22T21:34:24","date_gmt":"2016-02-22T21:34:24","guid":{"rendered":"https:\/\/www.mc.vanderbilt.edu\/vanderbiltmedicine\/?p=981"},"modified":"2021-08-11T19:41:09","modified_gmt":"2021-08-11T19:41:09","slug":"in-search-of-answers","status":"publish","type":"post","link":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/in-search-of-answers\/","title":{"rendered":"In Search of Answers"},"content":{"rendered":"
\"Illustration<\/a>
Illustration by Brad Yeo<\/figcaption><\/figure>\n

It\u2019s human nature to need answers. We don\u2019t like uncertainty.<\/p>\n

That includes getting answers about your health. You go to your health care provider; you want to leave with a diagnosis.<\/p>\n

But not all health care encounters work out that way. For about 25-30 million Americans, a diagnosis never comes, because the disease is rarely seen, previously undescribed or a rare form of a common disease. So the uncertainty continues. Visit after visit. Year after year.<\/p>\n

Now the odds of finding a diagnosis have improved. Vanderbilt University Medical Center is one of seven medical centers around the country in the Undiagnosed Diseases Network (UDN), a clinical research initiative of the National Institutes of Health (NIH).<\/p>\n

The Vanderbilt UDN clinical site will have emphases on heritable lung\u00a0diseases in adults and children,\u00a0heritable and other heart problems including pharmacogenetics,\u00a0arrhythmias and autonomic disorders in adults, and metabolic and other genetic problems in children.<\/p>\n

 <\/p>\n

Loss of Vision, Muscle Weakness, and No Diagnosis<\/strong><\/p>\n

Maggie Hall, 14, of Cookeville, Tennessee, is one of Vanderbilt\u2019s first UDN patients. She started wearing glasses when she was 5, and then developed weakness, exercise intolerance and worsening vision.<\/p>\n

\u201cWhen she was 8, basically over one day\u2019s time, her vision decreased significantly,\u201d said her father, Mike Hall. \u201cOne night we were throwing a football inside, and she wasn\u2019t even getting close to catching it. Then we played a board game and she couldn\u2019t find her piece on the board. We thought \u2018oh my gosh, what\u2019s going on?\u2019 and we started to panic.\u201d<\/p>\n

\"Photo<\/a>
Photo by Daniel Dubois<\/figcaption><\/figure>\n

There had been signs, Hall said. A couple of months before,\u00a0Maggie had been working on homework with her mother when she started to stumble over words and became nauseated. Then her vision blacked out. They rushed her to the hospital, but her vision came back. A CT scan failed to show a diagnosis.<\/p>\n

Several months later she had what her parents thought was a\u00a0migraine and loss of vision, and the vision never completely returned. She has some peripheral vision, but her central vision is gone. She was seen at Vanderbilt and then Emory. Steroids that were prescribed\u00a0didn\u2019t help.<\/p>\n

But along with decreasing vision, she also began experiencing intermittent muscle weakness. Although physicians believe her eyesight is an optic nerve issue, they don\u2019t know if the eyesight and muscle weakness are related.<\/p>\n

In the summer of 2014, Maggie became very weak. On a trip abroad with her father in Luxembourg, the weakness progressed and she had no appetite. She needed a wheelchair upon her return to the United States, but the weakness improved.<\/p>\n

\u201cShe had another episode in the fall of 2014. Maggie couldn\u2019t walk at school without getting winded and stopping to rest. She had tingling in her calves and numbness in her toes, was losing weight and needed help standing up.<\/p>\n

\u201cThat was a very tough year,\u201d Hall said.<\/p>\n

Maggie began seeing Tyler Reimschisel, M.D., a Vanderbilt professor of Pediatrics and Neurology and director of the Division of Developmental Medicine. She also visited the Mayo Clinic for help in diagnosing her illness. \u201cWe were starting to panic. Her health was going down, down, down,\u201d Hall said. Physicians ruled out multiple sclerosis and muscular dystrophy, and she had a muscle biopsy and a nerve conduction study performed to check muscle and nerve health. \u201cThey saw nerve death and muscle death, but also some regrowth,\u201d he said.<\/p>\n

Maggie\u2019s B12 levels were also very low\u2014about 90. Normal levels are 110-1,500 picograms per milliliter. Reimschisel\u2019s target for Maggie\u2019s level is 450. She has been getting B12 injections and vitamin cocktails, and her level is now approaching 400.<\/p>\n

For the Halls, not having a diagnosis hasn\u2019t been so much frustrating as \u201csad.\u201d \u201cAs long as she keeps doing fine, that\u2019s all that matters, but if having a diagnosis would help us treat it, then sure,\u201d Hall said. \u201cWe\u2019re very happy to be in this (UDN) program and see what comes up. I just want her to get better. But also, I\u2019m scared to find out what it is. I just want her to have a good life.\u201d<\/p>\n

Maggie, a high school freshman, attends Cookeville High School on an abbreviated schedule. She is assigned a helper to aid in getting from class to class. Hall said that Maggie has kept a positive attitude as her health has waxed and waned. She has a larger iPhone with enlarged type so she can see to text, and a device called a Merlin that electronically magnifies books on her computer monitor. \u201cShe can get around the house fine and she doesn\u2019t complain about her vision,\u201d he said.<\/p>\n

 <\/p>\n

Dedicated Detectives<\/strong><\/p>\n

For the past six years, prior to the formation of the UDN, hundreds of patients were evaluated in the Undiagnosed Diseases Program (UDP) at the NIH in Bethesda, Maryland. They have come from nearly every state, the District of Columbia and seven foreign countries.<\/p>\n

With the seven centers now accepting patients, the NIH has opened an online patient application portal called the UDN Gateway. Those ages 1 month to 99 years are eligible to be considered, and a doctor\u2019s recommendation is required. The Gateway replaces what had previously been a paper-and-mail application process.<\/p>\n

\"John<\/a>
John Phillips, M.D., with Vanderbilt\u2019s cryogenic storage system that contains not only cells, but clues to rare diseases. Photo by John Russell.<\/figcaption><\/figure>\n

\u201cThese are patients with mysteries that we are trying to solve,\u201d said John Phillips III, M.D., David T. Karzon Professor of Pediatrics and director of the Division of Medical Genetics and Genomic Medicine, who is co-principal investigator of the Vanderbilt UDN with John Newman, M.D., Elsa S. Hanigan Professor of Pulmonary Medicine. \u201cThe NIH\u2019s goal in this is to discover new diseases,\u201d Phillips said.<\/p>\n

\u201cA lot of these people haven\u2019t been diagnosed, not because they don\u2019t have something, but because nobody has seen what they have before. The demand has outgrown what NIH can offer (alone), and there\u2019s the convenience issue\u2014patients have to come from California to Bethesda. This network of clinical sites will serve that same role, but will be more geographically dispersed.\u201d<\/p>\n

Phillips said each clinical site in the UDN will offer studies that go beyond what is routinely done, such as whole exome sequencing (sequencing all genes).<\/p>\n

Newman said Vanderbilt was an ideal choice because of its structure and strengths in bioinformatics, its BioVU program (Vanderbilt\u2019s bank of de-identified DNA samples), the REDCap (Research Electronic Data Capture) developed at Vanderbilt, and the Clinical Research<\/p>\n

Center where patients will be seen.<\/p>\n

\u201cWe\u2019re very well positioned for this kind of work at Vanderbilt. This is what we do,\u201d he said.<\/p>\n

The six clinical sites (excluding the NIH site) in the UDN will\u00a0receive $43 million over four years and will contribute local medical\u00a0expertise and conduct clinical evaluation and scientific investigation in cases that involve patients with prolonged undiagnosed conditions.<\/p>\n

Since its 2008 launch, the UDN has reviewed more than 3,100 applications from patients around the world. More than 800 patients have been enrolled for a one-week evaluation.<\/p>\n

While approximately 25 percent of those have received some level of clinical, molecular or biochemical diagnosis, many patients remain undiagnosed.<\/p>\n

By including an additional six clinical sites, the 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 data. They will also benefit from common protocols designed to improve the level of diagnosis and care for patients with undiagnosed diseases.<\/p>\n

\"John<\/a>
John Newman, M.D., says Vanderbilt\u2019s structure and strength in bioinformatics make it an ideal member of the Undiagnosed Diseases Network. Photo by John Russell.<\/figcaption><\/figure>\n

By the summer of 2017, each new clinical site will accept about\u00a050 patients per year. The network has also brought on board two DNA sequencing facilities, one is at the Baylor College of Medicine, and the other is at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, partnering with Illumina in San Diego.<\/p>\n

 <\/p>\n

Putting a Name With a Disease<\/strong><\/p>\n

Between the launch of the UDN network in September 2015 and the end of January, 354 applications had been received and 41 of those were assigned to Vanderbilt. By early February, nine patients had been seen at Vanderbilt.<\/p>\n

Eighteen-year-old Rachel Barnett of Springfield, Tennessee, was one of them.<\/p>\n

Baye Barnett, Rachel\u2019s mother, doesn\u2019t know the cause of a complex set of physical problems that her daughter, Rachel, has battled since birth\u2014a heart defect, a low blood count that caused anemia, one kidney that doesn\u2019t function, high blood pressure, scoliosis and glaucoma. It seems like each doctor\u2019s visit uncovers a new problem, but no real answers for her puzzled family.<\/p>\n

Barnett said she is hoping to finally be able to put a name with Rachel\u2019s disease.<\/p>\n

The teenager was initially diagnosed with Diamond-Blackfan anemia, a disorder of the bone marrow, but that was later ruled out by her medical team at Vanderbilt.<\/p>\n

\u201cIt seems like something new turns up every time we take her to the doctor,\u201d Barnett said. \u201cWe\u2019ve just decided this is just Rachel. Every time we bring her to the doctor, we leave thinking \u2018maybe this is it.\u2019 But we may have to accept that we may not ever know.\u201d<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

It\u2019s human nature to need answers. We don\u2019t like uncertainty. That includes getting answers about your health. You go to your health care provider; you want to leave with a diagnosis. But not all health care encounters work out that way. For about 25-30 million Americans, a diagnosis never comes, because the disease is rarely…<\/p>\n","protected":false},"author":216,"featured_media":1040,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"_links_to":"","_links_to_target":""},"categories":[14,15,30],"tags":[],"class_list":["post-981","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-vm-features","category-vm-homepage-highlights","category-winter-2016"],"acf":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/cdn.vanderbilt.edu\/t2-main\/medschool-prd\/wp-content\/uploads\/sites\/82\/2016\/02\/udnslider.jpg","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/pcDnub-fP","_links":{"self":[{"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/posts\/981","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/users\/216"}],"replies":[{"embeddable":true,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/comments?post=981"}],"version-history":[{"count":1,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/posts\/981\/revisions"}],"predecessor-version":[{"id":3120,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/posts\/981\/revisions\/3120"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/media\/1040"}],"wp:attachment":[{"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/media?parent=981"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/categories?post=981"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medschool.vanderbilt.edu\/vanderbilt-medicine\/wp-json\/wp\/v2\/tags?post=981"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}