NIH recognizes undiagnosed diseases

By Ricki Lewis
If TV’s Dr. House, diagnostician extraordinaire, is ever truly stumped, he can refer his patient to the National Institutes of Health’s new "Undiagnosed Diseases Program."

Health care providers will refer patients whose symptoms do not fit any known pattern, and the agency will invite some of them for a work-up at the NIH’s Clinical Center in Bethesda. After examinations by dozens of medical specialists, patients might be enrolled in one of the existing 1,500 ongoing clinical trials or perhaps inspire a new investigation. In addition to attempting to diagnose the undiagnosable, the program will also identify subtypes of more common illnesses, leading to a “catalog of descriptions of conditions – a phenotype atlas that will provide new information for textbook diagnoses,” said William A. Gahl, MD, PhD clinical director at the National Human Genome Research Institute, who was one of a panel of speakers at a telephone news conference today announcing the program.

Amanda Young, a 26-year-old from Georgia, represented the type of patient who might take advantage of the new program. “I had horrible infections, and no one knew how to stop them. All they knew was that I had a low white blood cell count. By age 3 1/2 I’d had meningitis 3 times, seizures, and an abscess on my abdomen the size of a cantaloupe.” At age 8, a scratch on a leg turned into a raging infection, and gas gangrene led to amputation up to the hip. At age 9, she went to the NIH, and on May 13, 2003, her disease finally received a name: IRAK4 deficiency. She inherited a mutation from each parent, profoundly impairing her innate immunity.

The Undiagnosed Diseases Program anticipates 1-2 referrals a week for the first year, and hopefully many of them will hear “magic words” like Amanda Young did – a name for their diseases. More importantly will be the explanations that the names symbolize. For example, IRAK4 is an enzyme that participates in the Toll-like receptor pathway – discovered in the fruit fly Drosophila melanogaster.

As a former Drosophila geneticist, I was thrilled at the reference during the NIH phone conference to my old six-legged friends. I worked with homeotic mutants – flies that had legs in place of their antennae and mouthparts (that's a picture of one on the right). One reason that I left science for journalism was my oh-so-wrong feeling that flies with mixed up body parts mattered only to other flies. Months after I got my PhD, others in my lab discovered the homeobox – the genetic instructions for where organs end up in the embryo. Homeoboxes would eventually be found everywhere in the living world, from chickens to trees. And over the years, the mutations I’d worked with turned up behind a host of human diseases, from cancers, to birth defects, to curiously fused toes.

NIH’s Undiagnosed Diseases Program is a boon to desperately sick people, a fitting celebration of the 25 year anniversary of the Orphan Drug Act, and at the same time a vindication of basic research.

Lewis, R. Confessions of an ex-fly pusher. The Scientist 14(9):10, 2000.

Ricki Lewis is the author of the novel Stem Cell Symphony and the textbook Human Genetics: Concepts and Applications, now in its 8th edition. She is a fellow of the Alden March Bioethics Institute.

From http://blog.bioethics.net/2008/05/nih-recognizes-undiagnosed-diseases/