a researcher

Researchers in Thailand have established a rapid genetic sequencing program to improve the diagnosis of acutely ill children and adults.

Rapid diagnoses for severely ill patients enable targeted treatments that can save lives. However, many symptoms have a wide variety of potential causes, making diagnosis challenging.  

Rapid DNA sequencing has become a useful tool for diagnosis in critical care environments. Genetic diseases account for 14% of all diseases in newborns admitted to intensive care units and 1.9% in the case of adults. However, this technology has mostly been evaluated and performed in populations with European ancestry, especially in the United States, Europe and Australia. There remains a need to examine the clinical usefulness of this tool in people from different ethnicities and geographies.

To tackle this unmet need, a team of researchers from Chulalongkorn University, Bangkok, supported by colleagues from University College London, developed a rapid paediatric sequencing program to improve the diagnosis of acutely ill newborns, children and adults of Thai ethnicity. The project was supported by a grant from the UK’s Newton Fund.

“If we continue to use conventional diagnostic tests and fail to find a faster and more effective solution, many diagnoses, especially those of genetic diseases, will not be reached in time,” says Vorasuk Shotelersuk and Wuttichart Kamolvisit, paediatric geneticists at Chulalongkorn University. “We set up a rapid diagnostic testing system to avoid preventable deaths and improve treatment outcomes for patients.”

The researchers recruited 54 patients from 11 hospitals in Thailand, ranging in age from 2 days to 55 years. The study resulted in a successful genetic diagnosis for 25 patients (46%), covering 23 different diseases. The average time to a diagnosis was 12 days. The results led to a change in clinical management for 24 patients (44%), and improvement in clinical outcomes in 16 patients (30%).

For example, genetic sequencing was used to diagnose a 9-month-old girl presenting with rashes, an enlarged liver and pneumonia as having cystic fibrosis, which is a very rare condition for people of Thai ethnicity. The diagnosis enabled the team to change her treatment plan and avoid an invasive and unnecessary lung biopsy. The patient is now two years old and healthy, with no recurrent episodes of pneumonia.

Although genetic diseases account for only 1.9% of total hospitalized adult patients, the results of this study showed that adults may also benefit from genetic sequencing when they are in critical stages of undiagnosed genetic diseases. For example, in the case of a 24-year-old man presenting with schizophrenia, genetic sequencing revealed a diagnosis of methylmalonic aciduria and homocystinuria – conditions in which the body can't breakdown certain parts of proteins and fats. This led to a targeted treatment with two drugs that improved his neurological and psychiatric symptoms and enabled him to return to work.

More rapid and accurate diagnoses as a result of the project have improved treatment outcomes and quality of life for many patients. This has also helped to save money for individual families and the healthcare system.

In 2022, the project expanded to include 35 more cases from four more hospitals. 

“We are continually aiming to improve the accuracy and speed of diagnoses and to collaborate with more hospitals to bring the technology to more patients and save lives. Our ultimate goal is to end the diagnostic odyssey in patients who have had unknown conditions for several years,” says Shotelersuk. 

The team’s success has led to a broader and longer-term national project called the Genomics Thailand Initiative that was approved by the Thai cabinet in 2019 and granted a budget of approximately US$150 million for five years, from 2020 to 2024. Genomics Thailand aims to sequence the genomes of 50,000 Thais and build infrastructure to harness genomic information. The long-term hope is to provide better preventative information for Southeast Asian populations.

This work was supported by the Newton Fund Institutional Links grant, ID 216377911, under the Newton Fund. The grant is funded by the UK Department for Business, Energy and Industrial Strategy and Thailand Office of the Permanent Secretary, Ministry of Higher Education, Science, Research and Innovation, and delivered by the British Council. This work is also supported by the Newton Prize. For further information, please visit www.newtonfund.ac.uk