Increasing Diversity, Diagnostic Yield, and Efficiency in Clinical Evaluations of Rare Disorders

The University of Alabama at Birmingham (UAB) Undiagnosed Diseases Program (UAB UDP) was established as a fee-for-service clinical program in 2013 with support by UAB Medicine.

The program was accepted as an affiliate site of the UDN in 2022, fully IRB-approved in April 2023, and in Sep. 2023, was added as an X01 site.

The UAB UDP seeks to continue the affiliation, working within the UDN to provide services to groups in the Southeast and beyond who historically have not benefited from modern diagnostic investigations. The UAB UDP provides diagnostic evaluations for children and adults with chronic, undiagnosed diseases.

Patients are referred by physicians using HIPAA-compliant secure communications systems or are referred from the UDN through the UDN Gateway.

A UDP nurse practitioner contacts accepted patients for informed consent and works with the patient and the referring physician to collect and summarize medical records and obtain laboratory and imaging studies. A short summary is then produced, which is entered into the PhenoTips system, and data are shared with the UDN Gateway.

After physician review of the summary an in person or telemedicine appointment is made (billed to insurance) with the physician and any relevant specialist consultants. Laboratory tests and imaging studies are ordered as clinically indicated.

Progress in evaluations is reviewed by UAB UDP staff at monthly meetings, and a monthly conference is held with UDP staff and consultants to discuss ongoing unsolved cases. Genetic testing, including genome sequencing, is ordered if clinically indicated.

Patients who live in Alabama can be offered free-of-charge whole genome sequencing at HudsonAlpha Institute for Biotechnology under a state-supported program, the Alabama Genomic Health Initiative (AGHI).

HudsonAlpha is also able to do long-read sequencing in instances where a genetic diagnosis has not been achieved with short-read sequencing.

Several innovations are proposed which include increased use of telemedicine and a “genome-first” diagnostic approach, the inclusion of basic scientists in a set of diagnostic teams, collaboration with a federally qualified health center to increase diversity of patients seen, and incorporation of a set of bioinformatic and AI-powered tools to improve diagnostic success rates and reduce turnaround time.