Nettesheim Susanne, Kölker Stefan, Karall Daniela, Häberle Johannes, Posset Roland, Hoffmann Georg F, Heinrich Beate, Gleich Florian, Garbade Sven F
Division of Neuropediatrics and Metabolic Medicine, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Innsbruck, Austria.
Orphanet J Rare Dis. 2017 Jun 15;12(1):111. doi: 10.1186/s13023-017-0661-x.
Urea cycle disorders (UCDs) are a group of rare inherited metabolic disorders. Affected individuals often present with hyperammonemic encephalopathy (HE) and have an increased risk of severe neurologic disease and early death. The study aims to provide epidemiologic data and to describe the disease manifestation and short-term outcome.
Cross-border surveillance of newly diagnosed patients with UCDs - below 16 years of age - was performed from July 2012 to June 2015 in Germany and Austria and from January 2012 to December 2015 in Switzerland. Inquiries were sent monthly to all Pediatric Departments in Germany and Switzerland, and quarterly to the Austrian Metabolic Group. In addition, data were collected via a second source (metabolic laboratories) in all three countries.
Between July 2012 and June 2015, fifty patients (Germany: 39, Austria: 7, Switzerland: 4) with newly diagnosed UCDs were reported and later confirmed resulting in an estimated cumulative incidence of 1 in 51,946 live births. At diagnosis, thirty-nine patients were symptomatic and 11 asymptomatic [10 identified by newborn screening (NBS), 1 by high-risk-family screening (HRF)]. The majority of symptomatic patients (30 of 39 patients) developed HE with (n = 25) or without coma (n = 5), 28 of them with neonatal onset. Despite emergency treatment 15 of 30 patients with HE already died during the newborn period. Noteworthy, 10 of 11 patients diagnosed by NBS or HRF remained asymptomatic. Comparison with the European registry and network for intoxication type metabolic diseases (E-IMD) demonstrated that cross-national surveillance identified a higher number of clinically severe UCD patients characterized by earlier onset of symptoms, higher peak ammonium concentrations in plasma and higher mortality.
Cross-border surveillance is a powerful tool to identify patients with UCDs demonstrating that (1) the cumulative incidence of UCDs is lower than originally suggested, (2) the mortality rate is still high in patients with neonatal onset of symptoms, and (3) onset type and peak plasma ammonium concentration predict mortality.
尿素循环障碍（UCDs）是一组罕见的遗传性代谢紊乱疾病。受影响的个体常表现为高氨血症性脑病（HE），且患严重神经系统疾病和早亡的风险增加。本研究旨在提供流行病学数据，并描述疾病表现和短期预后。
2012年7月至2015年6月在德国和奥地利，以及2012年1月至2015年12月在瑞士，对新诊断的16岁以下UCD患者进行了跨境监测。每月向德国和瑞士的所有儿科部门发送询问函，每季度向奥地利代谢组发送询问函。此外，通过所有三个国家的第二个来源（代谢实验室）收集数据。
2012年7月至2015年6月期间，报告并随后确诊了50例新诊断的UCD患者（德国：39例，奥地利：7例，瑞士：4例），估计累积发病率为每51,946例活产中有1例。诊断时，39例患者有症状，11例无症状[10例通过新生儿筛查（NBS）确诊，1例通过高危家庭筛查（HRF）确诊]。大多数有症状的患者（39例中的30例）发生了HE，其中25例伴有昏迷，5例无昏迷，其中28例为新生儿期发病。尽管进行了紧急治疗，30例HE患者中有15例在新生儿期死亡。值得注意的是，11例通过NBS或HRF确诊的患者中有10例仍无症状。与欧洲中毒型代谢疾病登记处和网络（E-IMD）的比较表明，跨境监测发现了更多临床上严重的UCD患者，其特征为症状出现更早、血浆铵峰值浓度更高和死亡率更高。
跨境监测是识别UCD患者的有力工具，表明（1）UCD的累积发病率低于最初的推测，（2）症状在新生儿期出现的患者死亡率仍然很高，（3）发病类型和血浆铵峰值浓度可预测死亡率。
