Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, and net healthcare costs were reduced by $14,265 per child tested by URGS, RGS, or RES. URGS outperformed RGS and RES with faster time to diagnosis, and higher rate of diagnosis and clinical utility. Diagnostic and clinical outcomes will improve as methods evolve, costs decrease, and testing is implemented within precision medicine delivery systems attuned to ICU needs. URGS, RGS, and RES are currently performed in <5% of the ~200,000 children likely to benefit annually due to lack of payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition of possible genetic diseases, and current formatting as tests rather than as a rapid precision medicine delivery system. The gap between actual and optimal outcomes in children in ICUs is currently increasing since expanded use of URGS, RGS, and RES lags growth in those likely to benefit through new therapies. There is sufficient evidence to conclude that URGS, RGS, or RES should be considered in all children with diseases of uncertain etiology at ICU admission. Minimally, diagnostic URGS, RGS, or RES should be ordered early during admissions of critically ill infants and children with suspected genetic diseases.

单基因座（孟德尔）疾病是儿童住院、重症监护病房 (ICU) 入住、死亡率和医疗费用的主要原因。快速基因组测序（RGS）、超快速基因组测序（URGS）和快速外显子组测序（RES）是针对 ICU 患者遗传疾病的诊断测试。在 44 项针对 ICU 中患有不明病因疾病的儿童的研究中，37% 的儿童接受了基因诊断，26% 的儿童在管理上进行了相应的改变，通过 URGS、RGS 或 RES 测试，每个儿童的净医疗费用减少了 14,265 美元。URGS 优于 RGS 和 RES，诊断时间更快，诊断率和临床实用性更高。随着方法的发展、成本的降低以及在适应 ICU 需求的精准药物输送系统中实施测试，诊断和临床结果将得到改善。目前，由于缺乏付款人承保、报销不足、医院政策、住院医生不熟悉、对可能的遗传疾病认识不足以及目前的格式，每年约有 200,000 名可能受益的儿童中，URGS、RGS 和 RES 目前仅占不到 5%。测试而不是作为快速精准药物输送系统。由于 URGS、RGS 和 RES 的扩大使用滞后于可能通过新疗法受益的儿童的增长，因此 ICU 儿童的实际结果和最佳结果之间的差距目前正在扩大。有足够的证据表明，对于所有入院时患有不明病因疾病的儿童，应考虑 URGS、RGS 或 RES。至少，应在危重婴儿和疑似遗传病儿童入院时尽早进行诊断性 URGS、RGS 或 RES。