SC Connecticut News

As part of an ongoing effort at Yale School of Medicine (YSM) to better understand rare diseases, a team spanning multiple departments and specialties from YSM and Yale New Haven Hospital has received a grant of approximately $3.35 million from the National Institutes of Health (NIH) to join the Undiagnosed Diseases Network as a new Diagnostic Center of Excellence. The Yale Diagnostic Center of Excellence (YDCoE) will partner with key stakeholders in the community to increase genetic testing and diagnostic efforts in the Yale New Haven Health System and other health care systems in Connecticut for patients with unexplained or undiagnosed symptoms, especially those from underserved groups.

An estimated 300 million people worldwide are living with rare diseases, many of which are so uncommon that they may be entirely new to medicine and remain undiagnosed by clinicians for many years. These diseases, often genetic in origin, can cause severe physical and mental impairments that shorten lifespan and diminish quality of life. In the United States, rare diseases are defined as affecting fewer than 200,000 patients according to the 1983 Orphan Drug Act.

Rare diseases vary widely in their causes and symptoms. While some have characteristic features—for example, the “café-au-lait” spots that appear commonly on children with neurofibromatosis type 1—other rare diseases can be more difficult to identify. Many rare diseases often involve unexplained symptoms that don’t fit the criteria for more typical diagnoses.

“The challenge is there are so many diseases we have not even made a diagnosis for,” says Yong-Hui Jiang, MD, PhD, professor and chief of medical genetics at YSM and principal investigator of the new center. “In medicine, if you don’t know what a patient has, it’s very challenging to figure out how you can help them.”

There are 7,000 known rare diseases but only about 5% have treatments approved by the Food and Drug Administration. For many patients who are undiagnosed, treatment may be limited to symptom management. However, if a diagnosis is made, physicians may provide more targeted therapies—including new genetic therapies where appropriate—while avoiding unnecessary treatments.

The Undiagnosed Diseases Network (UDN) was established in 2013 by the NIH Common Fund with the goal of connecting research and clinical sites across the United States to better understand and treat patients with undiagnosed diseases. Undiagnosed diseases are defined as long-standing symptoms or elusive medical conditions that have not been diagnosed despite extensive clinical evaluation. The UDN has just entered its third phase in which over 20 clinical sites—including Yale—will apply their rare disease research with a particular focus on expanding access to underserved patient populations.

“We are excited to become a phase III new site for the UDN. It’s a significant honor for the community and for the hospital to be recognized for our many years of expertise based on our work on rare and undiagnosed diseases,” Jiang says.

Yale offers several innovative genetic diagnostic methods for rare diseases; one primary goal of the new center will be expanding these resources' availability for historically underserved groups.

“Over the past 15 years, advances in technology have offered numerous opportunities to figure out new diagnoses,” says Jiang. “Unfortunately, that benefit is unequal. Uninsured and minority populations have not benefitted to the same degree as populations with greater resources; we want to focus on these underserved individuals with this grant.”

Jiang's team will work with community-based organizations like Fair Haven Community Health Care (FHCHC), which cares for approximately 35,000 unique patients each year—the vast majority identifying as racial or ethnic minorities.

“We at Fair Haven Community Health Care are thrilled to partner with this team," says Benjamin Oldfield, MD, assistant clinical professor at YSM and vice president at FHCHC. "The work clearly aligns with our mission."

The YDCoE will also collaborate with Project Access New Haven providing patient navigation services and Transitions Clinical Network led by Emily Wang at YSM enrolling formerly incarcerated patients who typically lack easy access to diagnostic genetic services.

“It’s almost like a forgotten population,” Jiang notes.

One goal will be educational outreach efforts helping primary care physicians incorporate genetic screening into practice by educating them on likely rare diseases they might encounter early enough for timely intervention.

Over four years ahead YDCoE plans multi-tiered approach diagnosing suspected cases starting from reviewing medical records progressing through telemedicine appointments culminating into intensive evaluations including AI-enhanced diagnostics aimed increasing efficiency extracting relevant data guiding further steps making whole process streamlined according Jiang

One major barrier hindering progress remains funding scarcity due rarity low public health priority translating insufficient allocations both governmental pharmaceutical sectors impacting drug development potentiality

“When pharma looks at rare disease having half-million sufferers they're investing otherwise less inclined creating dilemma within community facing resource shortages interest gaps”

Joining UDN obtaining grants represents crucial strides scientifically clinically alike highlighting biological pathophysiological understanding alongside equitable patient care perspectives emphasizing necessity addressing unmet needs regardless prevalence

YDCoE constitutes collaborative endeavor involving numerous investigators consultants across various disciplines ensuring comprehensive concerted effort tackling complex challenges posed diverse spectrum seldom encountered ailments thereby contributing significantly towards advancing field enhancing overall healthcare delivery outcomes benefiting wider society ultimately fulfilling dual objectives knowledge generation therapeutic application aligned holistic vision envisaged broader scientific medical fraternity