Orphanet Journal of Rare Diseases, 2019. 14(1), 0-, DOI: https://doi.org/10.1186/s13023-019-1041-5

The Korean undiagnosed diseases program: lessons from a one-year pilot project

Soo Yeon Kim, Lim Byung Chan; Lee Jin Sook; Kim Woo Joong; Kim Hyuna; Ko Jung Min; Kim Ki Joong; Choi Sun Ah; Kim Hunmin; Hwang Hee; Choi Ji Eun; Cho Anna; Moon Jangsup; Seong Moon Woo; Park Sung Sup; Lee Yun Jeong; Kim Young Ok; Kim Jon Soo; Kim Won Seop; Kwon Yong Se; Park June Dong; Ahn Younjhin; Hwang Joo-Yeon; Park Hyun-Young; Lee Youngha; Choi Murim; Chae Jong-Hee

Abstract

Background: The Korean Undiagnosed Diseases Program (KUDP) was launched in January 2017 as a one-year pilotproject to address the increasing global interest in patients with undiagnosed rare diseases. The purpose of thispaper is to summarize the project results and emphasize the unmet research needs among patients with undiagnosedrare diseases in Korea.

Results: Patient enrollment, assessment, and diagnostic processes were determined by the KUDP clinical expertconsortium. Patients followed a diagnostic workflow after being categorized into one of four groups: I) insufficientclinical information or lack of standard diagnostic processes; II) undiagnosed due to low disease awareness; III) clinicallydiagnosed but unconfirmed genetically due to genetic heterogeneities; or IV) unknown disease due to complex,atypical clinical presentations. After excluding two patients from group I, 97 patients were enrolled, including 10 ingroup II, 67 in group III, and 20 in group IV. Most of them (92 of 97, 94.8%) were pediatric patients (< 18 years old) and59 (60.8%) were male. The primary symptoms for 80 patients (82.5%) were neurologic. During the one-year pilot study,72 patients completed a diagnostic assessment including clinical and molecular genetic analyses; some patients alsounderwent pathological or biochemical analysis. Twenty-eight of these patients (28/72, 38.9%) achieved moleculargenetic diagnosis. Thirteen patients were diagnosed based on traditional tests, including biochemical assay, single ortargeted genetic analysis, and chromosomal microarray. We performed whole exome sequencing on 52 patients, amongwhom 15 (28.8%, 15/52) reached a final diagnosis. One new disorder was identified via international collaboration.

Conclusions: Using an efficient clinical diagnostic workflow, this KUDP pilot study resulted in a fair diagnostic successrate, improving the potential for additional diagnoses and new scientific discovery of complex and rare diseases. KUDPalso satisfied unmet needs for rare diseases with multisystem involvement, highlighting the value of emerging genomictechnologies for further research into rare and still-undiagnosed conditions.

• DOI: https://doi.org/10.1186/s13023-019-1041-5
• ISBN or ISSN: 1750-1172

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.