SpainUDP: The Spanish Undiagnosed Rare Diseases Program

Area of Science:

• Rare disease diagnosis
• Genomic medicine
• Clinical genetics

Background:

• Delayed diagnosis is a significant challenge for rare undiagnosed diseases.
• The Spanish Undiagnosed Rare Diseases Program (SpainUDP) was established to address this unmet need, inspired by the US Undiagnosed Diseases Program (UDP).

Purpose of the Study:

• To describe the establishment and initial outcomes of the SpainUDP.
• To evaluate the multidisciplinary approach in diagnosing rare undiagnosed diseases.
• To highlight the importance of international data sharing in rare disease research.

Main Methods:

• Patients with undiagnosed diseases were referred to SpainUDP.
• Phenotypic information was standardized using Human Phenotype Ontology (HPO) and linked to whole-exome sequencing (WES) data.
• Participation in international initiatives (RD-Connect, Solve RD, UDNI, MME) facilitated global data sharing.

Main Results:

• Between late 2015 and early 2018, 147 cases were accepted, with 110 remaining after dropouts.
• Diagnosis was achieved in 20 out of 30 completed cases (67%).
• Ongoing studies include variant validation, WES, and deep phenotypic characterization.

Conclusions:

• SpainUDP successfully implements a multidisciplinary strategy for diagnosing rare undiagnosed diseases.
• The program aligns with International Rare Diseases Research Consortium (IRDiRC) goals for timely diagnosis and data sharing.
• International collaboration is crucial for advancing rare disease diagnosis and research.