Stevens Leah, Colglazier Elizabeth, Parker Claire, Amin Elena K, Nawaytou Hythem, Teitel David, Reddy Vadiyala M, Welch Carrie L, Chung Wendy K, Fineman Jeffrey R
Department of Pediatrics University of California San Francisco San Francisco California USA.
Department of Nursing University of California San Francisco San Francisco California USA.
Pulm Circ. 2022 Jan 18;12(1):e12033. doi: 10.1002/pul2.12033. eCollection 2022 Jan.
Despite therapeutic advances over the past decades, pulmonary arterial hypertension (PAH) and related pulmonary vascular diseases continue to cause significant morbidity and mortality in neonates, infants, and children. Unfortunately, an adequate understanding of underlying biology is lacking. There has been a growing interest in the role that genetic factors influence pulmonary vascular disease, with the hope that genetic information may aid in identifying disease etiologies, guide therapeutic decisions, and ultimately identify novel therapeutic targets. In fact, current data suggest that genetic factors contribute to ~42% of pediatric-onset PH compared to ~12.5% of adult-onset PAH. We report a case in which the knowledge that biallelic ATP13A3 mutations are associated with malignant progression of PAH in young childhood, led us to alter our traditional treatment plan for a 21-month-old PAH patient. In this case, we elected to perform a historically high-risk Potts shunt before expected rapid deterioration. Short-term follow-up is encouraging, and the patient remains the only known surviving pediatric PAH patient with an associated biallelic ATP13A3 mutation in the literature. We speculate that an increased use of comprehensive genetic testing can aid in identifying the underlying pathobiology and the expected natural history, and guide treatment plans among PAH patients.
尽管在过去几十年里治疗取得了进展，但肺动脉高压（PAH）及相关肺血管疾病在新生儿、婴儿和儿童中仍导致了显著的发病率和死亡率。不幸的是，目前对其潜在生物学机制仍缺乏充分了解。人们越来越关注遗传因素在肺血管疾病中所起的作用，希望遗传信息有助于确定疾病病因、指导治疗决策并最终确定新的治疗靶点。事实上，目前的数据表明，与成人发病的PAH中约12.5%的遗传因素贡献相比，遗传因素在儿童期发病的肺动脉高压（PH）中所占比例约为42%。我们报告了一个病例，由于了解到双等位基因ATP13A3突变与幼儿期PAH的恶性进展相关，我们改变了对一名21个月大的PAH患者的传统治疗方案。在这个病例中，我们选择在预期病情迅速恶化之前进行具有历史高风险的Potts分流术。短期随访结果令人鼓舞，该患者仍是文献中已知的唯一一名存活的患有双等位基因ATP13A3突变的儿童PAH患者。我们推测，增加全面基因检测的应用有助于识别潜在的病理生物学机制和预期的自然病程，并指导PAH患者的治疗方案。
