Asan Medical Center and National Institute of Health Succeed with Multidisciplinary Diagnostic Model to Prevent "Diagnostic Odyssey" in Rare Diseases

Development and Clinical Application of a Multidisciplinary Diagnostic Model

Rare genetic diseases are difficult to diagnose accurately due to the small number of patients and the lack of relevant information. Patients often have no choice but to visit multiple hospitals over periods ranging from several months to several years. Recently, in order to prevent this so-called "diagnostic odyssey," Asan Medical Center, in collaboration with the government and domestic medical institutions, developed a multidisciplinary diagnostic model for rare genetic diseases and achieved successful results in clinical practice.

From the left in the photo: Professor Beomhee Lee of the Medical Genetics Center at Asan Medical Center, Director Hyunyoung Park of the National Institute of Health, and Dr. Mihyun Park. Photo by Asan Medical Center

On August 6, Professor Beomhee Lee of the Medical Genetics Center at Asan Medical Center, Director Hyunyoung Park of the National Institute of Health, and Dr. Mihyun Park's team announced that after applying a genome analysis-based multidisciplinary diagnostic model to rare genetic disease patients with unknown diagnoses, one in four patients received a rapid diagnosis within two months.

To increase the diagnostic rate for rare disease patients, the research team established a diagnostic pipeline based on whole genome sequencing, in which doctors, geneticists, genetic counselors, and biologists collaborated organically. This approach included not only comprehensive diagnosis through genome analysis, but also family-based analysis, pre- and post-diagnostic genetic counseling, and subsequent clinical interventions.

To evaluate the clinical effectiveness of the diagnostic model, the research team applied it to 387 undiagnosed rare genetic disease patients and 514 family members at eight domestic medical institutions, including Asan Medical Center, from August to November 2023.

As a result, 27% (104 patients) of the participants were able to receive an accurate diagnosis within two months. Among those diagnosed, 77.9% were found to have either a single nucleotide variant in their DNA or an insertion or deletion in the DNA sequence. In addition, 40.7% were confirmed to have novel genetic variants that had not been previously reported in the medical literature, and 37.3% had newly arisen genetic variants in the affected child that were not present in the parents.

The diagnostic rate by age group was 30.6% for pediatric patients under 18 years old and 21.5% for adult patients 18 years or older, indicating a significantly higher diagnostic rate among pediatric patients. This is interpreted as being due to the fact that many genetic abnormalities manifest at a relatively young age.

Patients who had previously undergone genetic testing had a diagnostic rate of 34.9%, which was higher than the 20.3% diagnostic rate among patients who had never been tested.

The diagnostic rate was also higher for larger family units. When patients, parents, and siblings underwent genome analysis together, the diagnostic rate was 70%, compared to 15.8% when only the patient was tested. This is because the probability of diagnosing a genetic disease increases when the test is conducted as a family unit, including parents or siblings, rather than just the patient alone.

Among the participating patients, 4.7% (18 patients) were found to have incidental findings that were unrelated to their primary disease (the main symptom or condition for which they were originally tested) but could affect their future health.

Based on the results of genome analysis, the research team provided clinical interventions such as drug treatment, organ transplantation, and counseling for family planning to 150 patients. Among them, 68 patients received specialized genetic counseling. Through genetic counseling, patients were able to obtain detailed information about their diseases, as well as improve their emotional acceptance and disease management.

Professor Beomhee Lee of the Medical Genetics Center at Asan Medical Center stated, "Through this whole genome analysis-based multidisciplinary diagnostic model, we were able to discover new genetic variants in patient groups that were difficult to diagnose with conventional single-gene or patient-only testing. We also confirmed that genome analysis can contribute not only to diagnosis in clinical practice, but also to treatment decisions and family planning. If actively utilized in clinical settings in the future, it is expected to greatly improve the quality of life for many rare genetic disease patients who are struggling with diagnosis."

The results of this study were published in the latest issue of 'Clinical and Translational Medicine' (impact factor 6.9).

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