Vanderbilt University Medical Center, an original member institution of the National Institutes of Health’s Undiagnosed Diseases Network, (UDN) is launching its own program, the Vanderbilt Undiagnosed Diseases Program (VUDP), which will operate alongside the UDN. The VUDP goal is to expand services to many more patients who are living with the often-dire consequences of an undiagnosed disease.
The new program will allow VUMC, already a national leader in assisting adults and children with undiagnosed diseases, to help more patients and families who are struggling to find answers.
According to the National Institutes of Health, there are an estimated 30 million people in the United States with rare diseases, and as many as 1 in 10 are without a diagnosis. An undiagnosed disease can include a rare or newly described disease or a rare presentation of a more common disease. Between 70 and 80% of undiagnosed diseases are due to rare genetic disorders.
“The remarkable collaboration of our clinicians, geneticists, biostatisticians and others, and their amazing success with the NIH’s Undiagnosed Diseases Network fueled the desire to expand these efforts for patients and families. Many have lived in anguish while not knowing the true nature of their health problems or a way forward regarding possible treatments. Our mission with VUDP is to give these patients answers, hope and peace of mind,” said Jeff Balser, MD, PhD, President and Chief Executive Officer for VUMC and Dean of the Vanderbilt University School of Medicine.
Patients who have not been diagnosed have often been on a lengthy journey through the U.S. health system. Because nobody has seen their disease before, or through lack of access to expertise and advanced diagnostic modalities, they can remain undiagnosed for life.
“This program is driven by a passion to help patients coming to us in search of an answer. Many adult patients with undiagnosed diseases have been looking for answers for 10-20 years, and pediatric patients, all their lives. Emotionally, as you can imagine, it’s very tiring and there’s often a sense of hopelessness,” said Rizwan Hamid, MD, PhD, Dorothy O. Wells Professor of Pediatrics, director of Pediatric Medical Genetics and Genomic Medicine and director of the VUDP.
The VUDP will use Vanderbilt’s unique capabilities for analyzing genetic results, including its BioVU databank that allows for searches for genes and gene variants, Hamid said. “Leveraging resources like BioVU, the UDN program at VUMC has been extraordinarily successful. But we are very limited through the NIH program,” Hamid said. “We can only evaluate 30 patients a year — 15 adults and 15 children. On average, 10 patients are rejected or not evaluated for each patient who is accepted. At Vanderbilt we have incomparable expertise — an amazing collection of genomic resources, physicians and scientists. Why not make it available to more people?”
The new program will be a partnership between the Department of Pediatrics at Monroe Carell Jr. Children’s Hospital at Vanderbilt and the Department of Medicine at the Vanderbilt University Adult Hospital. “Our participation in the NIH program has been a wonderful example of this great collaborative spirit we have in our institution. The new program is another example of that,” Hamid said.
Since 2015, when the NIH-funded UDN program began enrolling patients, 202 patients from nine states have been accepted into Vanderbilt’s UDN, one of 12 clinical sites around the country working with four core labs to solve medical mysteries. Among all sites, the UDN has received 4,923 applications and 1,956 participants have been accepted. Of those, 1,525 have been evaluated and 467 participants have been diagnosed.
Hamid said the VUDP will begin with about one patient a week — the initial plan is to see 45-50 patients a year, with further expansion in the future. Like the NIH-funded program, medical records are submitted prior to the patient being seen, then it’s determined whether it’s likely the patient can be helped. The review starts with an initial medical records review, then those accepted consent to clinical testing and genomic sequencing (whole exome or whole genome), as well as an extensive inpatient clinical evaluation, which can often take up to five days.
“Since these are difficult cases, most will not be solved in that one-week period,” Hamid said. “The diagnostic odyssey from the time we see a patient until we get some sort of conclusion can sometimes take many months or longer.”
Hamid said patients are told from the beginning that they might not end up with an answer. “We tell them the success rate at Vanderbilt is very high, but they need to prepare themselves that even with all we can do, we may not find an answer for them. But we will do our best using the most cutting-edge informatics technology resources, some that are unique to Vanderbilt. If we find the answer, that’s fantastic, and sometimes, but not always, the answer allows us treat their condition.”
“The NIH-funded UDN program has been an enormous success at VUMC, with many patients receiving a definitive diagnosis and treatment plan after years in a diagnostic odyssey,” said Steven Webber, MBChB, MRCP, James C. Overall Professor, chair of the Department of Pediatrics and Pediatrician-in-Chief. “However, the number of patients that the program has been able to help has been limited based on the restrictions inherent to the program. This new clinical UDN program offers us the opportunity to offer VUMC’s expertise to many more patients who remain with chronic debilitating illness but without a clear diagnosis.”
Kimryn Rathmell, MD, PhD, Cornelius Abernathy Craig Professor of Medicine, chair of the Department of Medicine and Physician-in-Chief for the Vanderbilt University Adult Hospital and Clinics, said she is excited that this resource can be shared with a broader group of patients.
“This multidisciplinary, collaborative team is ready to take on the most challenging cases,” she said. “Our unity of clinical acumen with curiosity, and our depth in the cross-cutting fields of immunology, genetics and data science, make VUMC the place for diagnosis of complex diseases.”
The VUDP team consists of Hamid; John Phillips, MD, David T. Karzon Professor of Pediatrics and professor of Biochemistry, Medicine and Pathology; Joy Cogan, PhD, professor of Pediatrics; John Newman, MD, Elsa S. Hanigan Professor of Pulmonary Medicine; John Fahrenholz, MD, assistant professor of Medicine; Kevin Byram, MD, assistant professor of Medicine; Lisa Bastarache, MS, research assistant professor of Biomedical Informatics; Mary Koziura, DNP, FNP-BC; Anna Bican; and Jennifer Kennedy, CG.
For more information about the Vanderbilt Undiagnosed Diseases Program, including how to apply, visit: https://www.vanderbilthealth.com/service/undiagnosed-diseases-program.