To prevent patients with rare genetic diseases from undergoing a “diagnostic odyssey,” Asan Medical Center (AMC) has collaborated with the government and other medical institutions to develop a multidisciplinary diagnostic model, which is now applied in clinical settings, resulting in rapid diagnosis and other benefits.

AMC announced on Wednesday that Professor Lee Beom-hee of the Medical Genetics Center, along with Director Park Hyun-young and Dr. Park Mi-hyun of the National Institute of Health, applied a genome analysis-based multidisciplinary diagnostic model to patients with rare genetic diseases whose diagnoses were unknown.

The results showed that one in four patients received a rapid diagnosis within two months.

The research team established a diagnostic pipeline based on whole-genome sequencing (WGS), which analyzes the entire genome, to improve the diagnostic rate for patients with rare diseases. This pipeline involves collaborative efforts among physicians, geneticists, genetic counselors, and biologists.

The pipeline also includes comprehensive diagnosis through genome analysis, family-based analysis, pre- and post-diagnosis genetic counseling, and follow-up clinical interventions.

To evaluate the clinical efficacy of the diagnostic model, the research team applied it to 387 patients with undiagnosed rare genetic diseases and 514 family members from eight medical institutions in Korea, including AMC, from August to November 2023.

As a result, 104 patients (27 percent) received an accurate diagnosis within two months. Among the patients who received a diagnosis, 77.9 percent were found to have a single-letter mutation in deoxyribonucleic acid (DNA) or a mutation involving the insertion or deletion of a portion of the DNA sequence.

Besides, 40.7 percent were identified as new genetic mutations that had not been previously reported in the medical literature, and 37.3 percent were genetic mutations that were new to the patient but were present in the patient's parents.

The diagnosis rate by age was 30.6 percent for patients under 18 years of age and 21.5 percent for those 18 or older, with a significantly higher diagnosis rate among pediatric patients. This is attributed to the fact that many genetic disorders manifest at a relatively young age.

Patients with a history of genetic testing had a diagnosis rate of 34.9 percent, which was higher than the 20.3 percent diagnosis rate among patients who had not undergone testing.

Additionally, the diagnosis rate increased with larger family units. When patients underwent genomic testing with their parents and siblings, the diagnosis rate was 70 percent, significantly higher than the 15.8 percent when patients were tested alone. This suggests that the likelihood of diagnosing genetic disorders is higher when testing is conducted as part of a family unit, including parents or siblings, rather than when patients are tested individually.

Among the participants, 18 patients (4.7 percent) showed abnormal findings that could affect their future health, although these findings were unrelated to the primary disease that prompted the initial testing.

Based on the results of the genomic analysis, the research team provided clinical interventions, such as medication, organ transplantation, and family planning counseling, to 150 patients. Among them, 68 patients received professional genetic counseling. Through genetic counseling, patients were able to obtain detailed information about their diseases, which improved their emotional acceptance and disease management levels.

“Through this genome-wide analysis-based multidisciplinary diagnostic model, we were able to discover new genetic variants in patient groups that were difficult to diagnose using existing single-gene tests or individual patient tests. We also confirmed that genome analysis can contribute not only to diagnosis but also to treatment decisions and family planning in actual clinical practice,” Professor Lee said. “We expect that active utilization in clinical practice will greatly improve the quality of life for many patients with rare genetic diseases who currently face diagnostic challenges.”

The results of this study were published in the latest issue of Clinical and Translational Medicine (Impact Factor 6.9).