Clinical profiles and diagnostic challenges in 1158 children with rare hepatobiliary disorders
Clinical profiles and diagnostic challenges in 1158 children with rare hepatobiliary disorders
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DOI：
10.1038/s41390-020-0888-4
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发表时间：
2020-04-12
影响因子：
3.6
通讯作者：
Zhao, Pan
中科院分区：
文献类型：
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作者：
Dong, Yi;Wang, Jian;Zhao, Pan
背景罕见疾病的诊断在儿科肝病领域具有很大的挑战性，因为该领域的专家知识极其不足。这项研究旨在探索儿童罕见肝病的新发现并收集诊断经验。方法采用大样本病例分析研究方法，研究对象为有肝脏相关罕见疾病的儿科患者。所有病例均接受肝活检和/或基因测序。结果共确诊儿科患者1158例。肝源性遗传病最常见(737例)，其次为肝外或全身性肝损害(151例)和隐源性肝胆管异常(123例)。值得注意的是，根据遗传学结果结合临床指标对16名患者的诊断进行了重新评估。此外，101名接受基因测序的患者仍未得到诊断。在这些人中，55人的基因发现为阴性，30人的突变未能满足其典型的致病条件，16人检测到与临床指标不一致的变异。结论作为一项涉及已知数量最多的罕见肝胆疾病儿童的研究，它使我们能够积累关于这些疾病的病因和诊断的信息(特别是新的发现)。研究结果有助于提高人群的诊断质量。影响以肝脏为基础的遗传性疾病在儿童罕见肝病的临床特征中最为常见。在遗传性疾病中发现了一些新的变异(例如，在一例进行性家族性肝内胆汁淤积症2型患者中发现了c.3638G>；T和c.1435G>；C的两个变异)。作为一项涉及已知数量最多的罕见肝胆疾病儿科病例的研究，它使我们能够积累关于这些疾病的病因和诊断的信息。本研究有助于优化儿科肝病诊断流程，显著提高儿科肝病诊断质量。考虑到临床变异性通常存在于罕见的遗传病实体中，并且并不是所有的罕见疾病都是遗传性的，临床医生在诊断时不应过度依赖遗传结果。
Background Diagnosis of rare diseases possesses a great challenge in pediatric hepatology because expert knowledge in the field is extremely insufficient. The study aims to explore new findings and collect diagnostic experience from pediatric rare liver diseases. Methods The large-sample case analysis study included pediatric patients who had liver-involved rare diseases. All cases underwent liver biopsy and/or gene sequencing. Results A total of 1158 pediatric patients were identified. Liver-based genetic diseases were most frequent (737 cases), followed by liver damages involved in extrahepatic or systemic disorders (151 cases) and cryptogenic hepatobilliary abnormalities (123 cases). Of note, diagnoses of 16 patients were re-evaluated according to genetic results combined with clinical pointers. In addition, 101 patients who underwent gene sequencing remained undiagnosed. Of them, 55 had negative genetic findings, 30 harbored mutations that failed to meet their typically pathogenic condition, and 16 had detected variants that were inconsistent with clinical pointers. Conclusions As a study involving known largest number of children with rare hepatobiliary disorders, it allows us to accumulate information (especially new findings) on the etiology and diagnosis of these disorders. The results can help to improve the diagnostic quality in the population. ImpactLiver-based genetic diseases were most frequent in clinical profiles of pediatric rare liver diseases. Some novel variants in cases with genetic diseases (for example, two variants of c.3638G>T and c.1435G>C in a patient with progressive familial intrahepatic cholestasis type 2) were identified. As a study involving known largest number of pediatric cases with rare hepatobiliary disorders, it allows us to accumulate information on the etiology and diagnosis of these disorders. The study can help to optimize the diagnostic process and significantly improve the diagnostic quality in the field of pediatric hepatology. Given that clinical variability often exists within rare genetic disease entities and not all rare disorders are genetic, clinicians should not over-depend on the genetic results in the diagnosis.