Undiagnosed Diseases Network

Undiagnosed Diseases Network (UDN) is a research initiative established to improve the level of diagnosis and care for patients with rare diseases and conditions that remain undiagnosed despite extensive medical evaluation. The UDN operates through a network of clinical sites across the United States, leveraging a collaborative model that brings together experts in genetics, bioinformatics, and various medical specialties to solve challenging medical mysteries. The network aims to both provide answers to patients with unknown conditions and advance medical knowledge about rare and novel diseases.

Background

The UDN originated from the success of the Undiagnosed Diseases Program (UDP) at the National Institutes of Health (NIH) in Bethesda, Maryland. Recognizing the need to expand the program's reach and capabilities, the NIH launched the UDN in 2014 with funding from the National Human Genome Research Institute (NHGRI), the National Center for Advancing Translational Sciences (NCATS), and other NIH components. The initiative represents a significant effort to use integrated clinical and research approaches to uncover diagnoses for patients who have eluded diagnosis for years.

Goals

The primary goals of the UDN include:

• Providing a diagnosis for patients with previously undiagnosed diseases.
• Facilitating better understanding of novel and rare diseases.
• Advancing medical knowledge and technologies to improve diagnosis and treatment of these challenging conditions.

Structure

The UDN is composed of several key components:

• Clinical Sites: Hospitals and medical centers across the U.S. that evaluate patients using a comprehensive, multidisciplinary approach.
• The Coordinating Center: Manages patient applications, coordinates network activities, and facilitates data sharing among clinical sites and with the broader medical and research communities.
• The Sequencing Core: Provides state-of-the-art genomic sequencing and analysis to identify potential genetic causes of patients' conditions.
• Model Organisms Screening Center (MOSC): Uses model organisms to study gene function and to validate the pathogenicity of genetic variants.
• Metabolomics Core: Analyzes small molecule metabolites that may provide insights into disease mechanisms and potential treatments.

Process

Patients seeking evaluation by the UDN must first submit an application through the UDN website. Applications are reviewed for eligibility based on specific criteria, including the extent of prior medical evaluation and the presence of a condition that remains undiagnosed. Accepted patients are then evaluated at one of the UDN's clinical sites, where they undergo a comprehensive review of their medical history, physical examinations, and a variety of specialized tests, which may include genomic sequencing and metabolomic analysis.

Impact

Since its inception, the UDN has accepted hundreds of patients, many of whom have received a diagnosis for the first time. These diagnoses not only provide answers to patients and their families but also contribute to the broader understanding of rare and novel diseases. The findings from UDN investigations have led to the publication of numerous case reports and research articles, advancing the field of rare disease research and diagnostics.

Challenges and Future Directions

Despite its successes, the UDN faces challenges, including the need for sustainable funding and the ongoing challenge of interpreting complex genetic data. As the network continues to evolve, it aims to expand its reach, improve diagnostic technologies, and enhance collaboration with researchers and clinicians worldwide to benefit more patients with undiagnosed diseases.

NIH genetic and rare disease info

• NIH info on Undiagnosed Diseases Network

Undiagnosed Diseases Network is a rare disease.