On May 19, 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was launched to address an unmet need in the US health care system, ie, the diagnosis of mysterious, often multisystem diseases. A prime mover in initiating the program was the recognition by the NIH Office of Rare Diseases Research that it took 1 to 5 years to reach a proper diagnosis for 33% of patients with rare disorders and more than 5 years for 15% of these patients.1 Moreover, at least 6% of the inquiries to the Genetic and Rare Diseases Information Center were from individuals still seeking a diagnosis. A second critical motivation for establishing the program was to discover new diseases that would provide medically relevant insights into biochemistry, physiology, and cell biology. After receiving $280 000 in funding from the Office of Rare Diseases Research, and with the support of the National Human Genome Research Institute and the NIH Clinical Center, the program's popularity and publicity increased rapidly, and the budget was increased to $1.9 million in fiscal year 2009 and to $3.5 million annually for fiscal years 2010 through 2012.
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