Queensland Paediatric Immunology and Allergy Service, Children's Health Queensland, Brisbane, QLD, 4101, Australia.
The Frazer Institute, Dermatology Research Centre, The University of Queensland, Brisbane, QLD, 4102, Australia.
Eur J Hum Genet. 2023 Oct;31(10):1125-1132. doi: 10.1038/s41431-023-01321-z. Epub 2023 Mar 3.
Molecular diagnosis of paediatric inborn errors of immunity (IEI) influences management decisions and alters clinical outcomes, through early use of targeted and curative therapies. The increasing demand for genetic services has resulted in growing waitlists and delayed access to vital genomic testing. To address this issue, the Queensland Paediatric Immunology and Allergy Service, Australia, developed and evaluated a mainstreaming model of care to support point-of-care genomic testing for paediatric IEI. Key features of the model of care included a genetic counsellor embedded in the department, state-wide multidisciplinary team meetings, and variant prioritisation meetings to review whole exome sequencing (WES) data. Of the 62 children presented at the MDT, 43 proceeded to WES, of which nine (21%) received a confirmed molecular diagnosis. Changes to treatment and management were reported for all children with a positive result, including curative hematopoietic stem cell transplantation (n = 4). Four children were also referred for further investigations of variants of uncertain significance or additional testing due to ongoing suspicion of genetic cause after negative result. Demonstrating engagement with the model of care, 45% of the patients were from regional areas and on average, 14 healthcare providers attended the state-wide multidisciplinary team meetings. Parents demonstrated understanding of the implications of testing, reported minimal decisional regret post-test, and identified benefits to genomic testing. Overall, our program demonstrated the feasibility of a mainstreaming model of care for paediatric IEI, improved access to genomic testing, facilitated treatment decision-making, and was acceptable to parents and clinicians alike.
儿科遗传性免疫缺陷病 (IEI) 的分子诊断通过早期使用靶向和治愈性治疗来影响管理决策并改变临床结果。对遗传服务的需求不断增加，导致候补名单不断增加，进而延误了重要基因组检测的机会。为了解决这个问题，澳大利亚昆士兰州儿科免疫学和过敏服务中心开发并评估了一种主流护理模式，以支持儿科 IEI 的即时基因组检测。该护理模式的主要特点包括部门内嵌入的遗传咨询师、全州多学科团队会议以及变体优先级会议，以审查全外显子组测序 (WES) 数据。在 MDT 上呈现的 62 名儿童中，有 43 名接受了 WES 检测，其中 9 名（21%）获得了明确的分子诊断。所有阳性结果的儿童都报告了治疗和管理方面的变化，包括治愈性造血干细胞移植（n=4）。由于阴性结果后仍持续怀疑遗传原因，有 4 名儿童还被转介进行进一步的不确定意义变异或额外检测。有 45%的患者来自偏远地区，并且全州多学科团队会议平均有 14 名医疗保健提供者参加，这表明患者参与了该护理模式。父母对检测的影响表示理解，报告的测试后决策后悔最小，并认为基因组检测有好处。总体而言，我们的项目证明了儿科 IEI 的主流护理模式是可行的，改善了基因组检测的可及性，促进了治疗决策，并得到了家长和临床医生的认可。
