Vasquez-Loarte Tania, Thompson John D, Merritt J Lawrence
Public Health Genetics, University of Washington, Seattle, WA 98195, USA.
Newborn Screening Laboratory, Public Health Laboratories, Washington State Department of Health, Shoreline, WA 98155, USA.
Int J Neonatal Screen. 2020 Oct 8;6(4):77. doi: 10.3390/ijns6040077.
Proximal urea cycle disorders (PUCDs) have adverse outcomes such as intellectual disability and death, which may benefit from newborn screening (NBS) through early detection and prevention with early treatment. Ornithine transcarbamylase deficiency (OTCD) and carbamoyl phosphate synthetase 1 deficiency (CPS1D) are screened in six and eight states in the United States. We analyzed current evidence to see if it supports inclusion of PUCDs in the NBS panels based upon prevention potential, medical, diagnostic, treatment, and public health rationales. A literature review was performed in PubMed using MESH terms for OTCD, CPS1D, and NAGSD. A systematic review was performed in the hallmark of NBS inclusion criteria. We reviewed 31 articles. Molecular and biochemical diagnosis is available to provide diagnostic evidence. Untreated PUCDs have a significant burden with considerable developmental delay and mortality that may improve with early treatment. Tandem mass spectrometry can be used for NBS for PUCDs; however, citrulline and glutamine alone are not specific. Medical treatments currently available for PUCDs meet existing medical, diagnostic, treatment, and public health rationales. Improvement in NBS algorithms to increase sensitivity and specificity will allow earlier diagnosis and treatment to potentially improve disability and mortality rates.
近端尿素循环障碍（PUCDs）会导致智力残疾和死亡等不良后果，通过新生儿筛查（NBS）进行早期检测并通过早期治疗加以预防可能会带来益处。在美国，鸟氨酸转氨甲酰酶缺乏症（OTCD）和氨甲酰磷酸合成酶1缺乏症（CPS1D）分别在六个和八个州进行筛查。我们分析了现有证据，以确定其是否支持基于预防潜力、医学、诊断、治疗及公共卫生依据将PUCDs纳入新生儿筛查项目。在PubMed中使用OTCD、CPS1D和NAGSD的医学主题词进行了文献综述。对新生儿筛查纳入标准的标志性内容进行了系统综述。我们查阅了31篇文章。可通过分子和生化诊断提供诊断证据。未经治疗的PUCDs负担沉重，伴有明显的发育迟缓及死亡率，早期治疗可能会改善这种情况。串联质谱可用于PUCDs的新生儿筛查；然而，仅瓜氨酸和谷氨酰胺并不具有特异性。目前可用于PUCDs的医学治疗符合现有的医学、诊断、治疗及公共卫生依据。改进新生儿筛查算法以提高敏感性和特异性将有助于更早诊断和治疗，从而有可能改善残疾率和死亡率。
