Rapid exome sequencing as the first‐tier investigation for diagnosis of acutely and severely ill children and adults in Thailand

Abstract

The use of rapid DNA sequencing technology in severely ill children in developed countries can accurately identify diagnoses and positively impact patient outcomes. This study sought to evaluate the outcome of Thai children and adults with unknown etiologies of critical illnesses with the deployment of rapid whole exome sequencing (rWES) in Thailand. We recruited 54 unrelated patients from 11 hospitals throughout Thailand. The median age was 3 months (range, 2 days–55 years) including 47 children and 7 adults with 52% males. The median time from obtaining blood samples to issuing the rWES report was 12 days (range, 5–27 days). A molecular diagnosis was established in 25 patients (46%), resulting in a change in clinical management for 24 patients (44%) resulting in improved clinical outcomes in 16 patients (30%). Four out of seven adult patients (57%) received the molecular diagnosis which led to a change in management. The 25 diagnoses comprised 23 different diseases. Of the 34 identified variants, 15 had never been previously reported. This study suggests that use of rWES as a first‐tier investigation tool can provide tremendous benefits in critically ill patients with unknown etiology across age groups in Thailand.

Measures of Utility Among Studies of Genomic Medicine for Critically Ill Infants

“…Twenty-two articles met our eligibility criteria ( Figure 1 ). 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 All but 1 study 46 included some measure of utility (although authors used different terms for this concept, such as usefulness 35 or impact on medical decision-making 31 ) and therefore were included in subsequent analysis. Included studies reflected results from a total of 1654 patients.…”

“…Included studies reflected results from a total of 1654 patients. Most studies (18 [86%]) 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 43 , 44 , 45 took place in both neonatal and pediatric intensive care units, and inclusion criteria for participants ranged from specific (eg, a suspected known monogenic disorder) to broad (eg, unknown etiology of disease) (eTable in the Supplement ). The studies contained a mean of 79 patient cases (range, 7-354 patient cases).…”

“…In 9 studies (43%), secondary findings were reported to families, 27 , 28 , 29 , 35 , 36 , 40 , 41 , 43 , 44 whereas in 6 studies (29%), they were not 25 , 30 , 31 , 32 , 33 , 38 ; the remaining 6 studies (29%) provided no information about management of secondary findings. 26 , 34 , 37 , 39 , 42 , 45 …”

“…For example, changes in patient care did not necessarily correlate with benefit as perceived by patients, families, or physicians and should be considered a surrogate rather than primary marker of benefit. 7 , 47 Only the studies by Dimmock et al 40 , 41 and Kamolvisit et al 45 attempted to record whether the change was expected to benefit the patient and family. Of note, Dimmock et al 41 reported that with 1 exception, “changes in longer-term outcomes were deemed too speculative to be confident about cost savings or improved quality of life beyond the initial episode of care.” To make this more concrete, if 1 diagnosis informs prescribing of a new drug that largely alleviates the infant’s symptoms and another diagnosis affirms continuation of a drug that only moderately decreases symptoms, these changes are recorded as equally beneficial in currently used measures of utility; however, most physicians and families would likely value the former more highly than the latter.…”

Genetic basis of sudden death after COVID-19 vaccination in Thailand

“…A total of 13 variants in 7 genes were identified by WES in 11 of 13 cases (85%), compared with approximately one-third to one-half of the diagnostic yield of WES for patients with previously undiagnosed diseases. 10,11 This suggests that SUD after COVID-19 vaccination may have a genetic susceptibility more commonly identified by WES, compared with other rare and undiagnosed diseases.…”