Japan has a long history of tackling hard to diagnose rare diseases (called Nan-Byo in Japanese for “difficult illness”, literally). The first public definition for Nan-Byo appeared in 1972. Since then the Ministry of Health, Labour and Welfare (MHLW) has played a key role in supporting Rare Diseases (RD) research, enabling the number of designated Nan-Byo to rise from 4 in 1972 to 56 in 2014, and is expected to be 330 in 2017. Despite these efforts, a vast majority of Nan-Byo patients are still struggling to obtain a diagnosis and eventually a treatment; known metaphorically as “the diagnostic odyssey”. A network has now been created to ensure systematic diagnosis by medical experts through phenotypic and genetic data matching.
In collaboration with RD researchers and the Japanese universal healthcare system, the Japan Agency for Medical Research and Development (AMED) launched the Initiative on Rare and Undiagnosed Diseases (IRUD) in 2015. The rational here is to accelerate the pioneering efforts made within the international community such as the Undiagnosed Diseases Program/Network (UDP/UDN) in the USA, the Finding of Rare Disease Genes (FORGE) in Canada, and the Deciphering Developmental Disorders (DDD) in UK. Japan also strongly supported for years the development of Next Generation Sequencing (NGS), thus facilitating the use of whole-exome and whole-genome analyses to diagnose RD patients.
For two years, IRUD has built (and will continue) a growing network composed of medical experts and the patients themselves. These efforts have led to the construction of a nationwide medical research consortium dedicated to helping these patients receive diagnoses. The network enables primary healthcare clinics to collaborate with more than 400 hospitals including 34 IRUD Clinical Centers. Patients are referred to these IRUD Clinical Centers when the patient remains undiagnosed for 6 months AND shows a sign of either an affection of more than one organ or a disease with a genetic etiology. Complex cases can thus be reviewed by multi-disciplinary IRUD Diagnosis Committees made up of medical specialists and clinical geneticists. This process is supported by 4 IRUD Analysis Centers which administer genetic tests, including whole-exome or whole-genome sequencing. After the committee’s discussion, genetic counselors provide feedback to individual patients.
The IRUD Data Center is storing all clinical and genetic data gathered in for each patient in a globally compatible patient-matching system, enabling data to be exchanged, upon consent, with domestic and overseas medical organizations. As a consequence, the chances of successful diagnosis increase with the possibility to compare data of a broader pool of patients.
For the future, IRUD will continue to expand its nationwide network by recruiting more local collaborators and to increase patients’ participation by disseminating widely its actions to hospitals, clinicians and municipalities. In addition, IRUD and AMED join forces to strengthen their collaboration with international organizations, for instance, through the IRDiRC consortium.
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