University of Utah School of Medicine, Salt Lake City, UT.
Division of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Primary Children's Hospital, Salt Lake City, UT; Center for Personalized Medicine, Primary Children's Hospital, Salt Lake City, UT.
J Pediatr. 2023 Sep;260:113534. doi: 10.1016/j.jpeds.2023.113534. Epub 2023 Jun 2.
To describe the usefulness of rapid whole genome sequencing (rWGS) in a cohort of children presenting with acute liver dysfunction.
This was a retrospective, population-based cohort study conducted at Primary Children's Hospital in Salt Lake City, Utah. Children meeting criteria for acute liver dysfunction who received rWGS between August 2019 and December 2021 were included. rWGS was performed on blood samples from the patient and parents (1 or both depending on availability). The clinical characteristics of patients with positive rWGS results were compared with those with negative results.
Eighteen patients with pediatric acute liver dysfunction who had rWGS were identified. The median turnaround time from the date rWGS testing was ordered to the date an initial report was received was 8 days with a shorter turnaround time in patients with a diagnostic rWGS (4 days vs 10 days; P = .03). A diagnostic result was identified in 7 of 18 patients (39%). Subsequently, 4 patients in this cohort, who had negative rWGS results, were found to have a toxic exposure accounting for their liver dysfunction. With removal of these patients, the diagnostic rate of rWGS was 7 of 14 (50%). The use of rWGS led to a change in management for 6 of 18 patients (33%).
We found that rWGS provided a diagnosis in up to 50% of pediatric acute liver dysfunction. rWGS allows for higher diagnostic rates in an expedited fashion that affects clinical management. These data support the routine use of rWGS for life-threatening disorders in children, specifically acute liver dysfunction.
描述快速全基因组测序（rWGS）在一组表现为急性肝功能障碍的儿童中的应用价值。
这是一项在犹他州盐湖城的Primary Children's Hospital 进行的回顾性、基于人群的队列研究。纳入了 2019 年 8 月至 2021 年 12 月期间接受 rWGS 的符合急性肝功能障碍标准的儿童。rWGS 是在患者和家长的血液样本上进行的（根据可用性，1 份或 2 份都做）。比较了 rWGS 阳性结果患者与阴性结果患者的临床特征。
确定了 18 例患有儿科急性肝功能障碍的患者进行了 rWGS。从 rWGS 检测开始到收到初始报告的时间中位数为 8 天，诊断性 rWGS 的周转时间更短（4 天比 10 天；P = 0.03）。18 例患者中有 7 例（39%）确定了诊断结果。随后，在 rWGS 结果为阴性的这组患者中，有 4 例发现了导致其肝功能障碍的毒性暴露。去除这些患者后，rWGS 的诊断率为 14 例中的 7 例（50%）。rWGS 的使用导致 18 例患者中的 6 例（33%）的治疗方案发生了改变。
我们发现 rWGS 可在高达 50%的儿科急性肝功能障碍患者中提供诊断。rWGS 以加快速度提供更高的诊断率，从而影响临床管理。这些数据支持在危及生命的儿童疾病中常规使用 rWGS，特别是急性肝功能障碍。
