1/ Quick thread on our paper published yesterday from the Undiagnosed Diseases Network nejm.org/doi/full/10.10…
2/ We analyzed data from the first 1519 patients referred over 20 months. We report rates of diagnosis, how those diagnoses were made, and the medical impact of the diagnosis.
3/ The network is open to anyone with an undiagnosed disease anywhere in the world. Patients can self-refer or be referred through our website. Care is provided at no cost to the patient.
undiagnosed.hms.harvard.edu
undiagnosed.hms.harvard.edu
4/ The network comprised: 7 clinical sites, 2 sequencing cores, a metabolomics core, a model organisms core, and a coordinating center. We recently expanded. nih.gov/news-events/ne… 
5/ The acceptance rate was 40%. The most common primary symptom categories were neurological, rheumatological/immunological, and musculoskeletal. A little over half were pediatric cases.
6/ Although 32% of accepted applicants had already undergone exome sequencing at the time of referral, we achieved a diagnostic rate of 35%. Of these diagnoses, 11% were made by clinical evaluation alone, 74% were made by exome or genome sequencing.
7/ For those with prior exome, ~1/3 diagnosed by re-analysis; ~2/3 via further sequencing. Common reasons for success: new knowledge, better genome coverage, trio/quartet sequencing, mosaicism. All diagnoses in supplement ->
nejm.org/doi/suppl/10.1…
nejm.org/doi/suppl/10.1…
8/ 80% of diagnoses led to changes in medical management: 21% therapy, 37% testing, 36% counseling. Therapies included known drugs in almost 80% of cases.
9/ Diagnoses were classified in various ways according to whether a new symptom complex or a new gene/region were identified. A total of 31 new syndromes were defined.
10/ Healthcare costs pre- and post-UDN were dramatically different
11/ Hopefully you feel we did ok - these patients started with no answers - but we have a lot more work to do! We need better sequencing, clinically focused algorithms, more omics integration, and more efficient translation to therapy.
nature.com/articles/nrg.2…
nature.com/articles/nrg.2…
12/ Truly an honor to co-chair this special group of people during this period with the amazing Bill Gahl. Traditional clinical skills + cutting edge science to try to help patients with nowhere else to turn…the privilege of a lifetime. /fin
