Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
Division of Pediatric Cardiology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
Cold Spring Harb Mol Case Stud. 2024 Jan 10;9(4). doi: 10.1101/mcs.a006292. Print 2023 Dec.
Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.
肺泡毛细血管发育不良（ACD）是一种致命的疾病，通常在新生儿期表现为难治性低氧血症和肺动脉高压。传统上需要进行肺活检来确立诊断。我们报告了一名 22 个月大的男性，他因贫血、严重肺动脉高压和右心衰竭而就诊。他的病情复杂，导致心脏骤停和需要体外膜氧合。胸部计算机断层扫描显示肺间质隔增厚和肺水肿的异质性模式。他的病情病因不明，由于身体脆弱，肺活检被禁止，并且进行了讨论以转至姑息治疗。进行了快速全基因组测序（rWGS）。在 2 天内，结果显示出一种新的 基因致病性变异，导致疑似非典型 ACD 的诊断。已经报道了使用药物治疗或肺移植存活的非典型 ACD 病例。基于 rWGS 诊断和非典型 ACD 更有利的潜在情况，进行了积极的药物治疗。患者在医院住院 67 天后出院；他目前情况良好，在最初就诊后超过 30 个月，仅随后住院一次，无需进行肺移植。我们的病例揭示了 rWGS 在诊断未知的危重症儿童中的潜在应用。rWGS 和其他先进的遗传测试可以指导临床管理，并扩大我们对非典型 ACD 和其他疾病的认识。
