• En-Ting Wu, Wuh-Liang Hwu, Yin-Hsiu Chien, Ching Hsu, Ting-Fu Chen, Nai-Qi Chen, Hung-Chieh Chou, Po-Nien Tsao, Pi-Chuan Fan, I-Jung Tsai, Shuan-Pei Lin, Wu-Shiun Hsieh, Tung-Ming Chang, Chi-Nien Chen, Chen-Hao Lee, Yen-Yin Chou, Pao-Chin Chiu, Wen-Hui Tsai, Hann-Chang Hsiung, Feipei Lai, and Ni-Chung Lee.
• Department of Paediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
• Pediatr Crit Care Me. 2019 Nov 1; 20 (11): 1021-1026.

ObjectivesCritical illnesses caused by undiagnosed genetic conditions are challenging in PICUs. Whole-exome sequencing is a powerful diagnostic tool but usually costly and often fail to arrive at a final diagnosis in a short period. We assessed the feasibility of our whole-exome sequencing as a tool to improve the efficacy of rare diseases diagnosis for pediatric patients with severe illness.DesignObservational analysis.MethodWe employed a fast but standard whole-exome sequencing platform together with text mining-assisted variant prioritization in PICU setting over a 1-year period.SettingA tertiary referral Children's Hospital in Taiwan.PatientsCritically ill PICU patients suspected of having a genetic disease and newborns who were suspected of having a serious genetic disease after newborn screening were enrolled.InterventionsNone.Measurements And Main ResultsAround 50,000 to 100,000 variants were obtained for each of the 40 patients in 5 days after blood sampling. Eleven patients were immediately found be affected by previously reported mutations after searching mutation databases. Another seven patients had a diagnosis among the top five in a list ranked by text mining. As a whole, 21 patients (52.5%) obtained a diagnosis in 6.2 ± 1.1 working days (range, 4.3-9 d). Most of the diagnoses were first recognized in Taiwan. Specific medications were recommended for 10 patients (10/21, 47.6%), transplantation was advised for five, and hospice care was suggested for two patients. Overall, clinical management was altered in time for 81.0% of patients who had a molecular diagnosis.ConclusionsThe current whole-exome sequencing algorithm, balanced in cost and speed, uncovers genetic conditions in infants and children in PICU, which helps their managements in time and promotes better utilization of PICU resources.

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