Welcome to Chinese Journal of Evidence-Based Pediatrics,Today is
中文版

Chinese Journal of Evidence -Based Pediatric ›› 2019, Vol. 14 ›› Issue (1): 1-7.

• Original Papers •     Next Articles

The diagnosis of inherited metabolic disorders in high risk neonates: mass spectrometry and high throughput sequencing

XU Su-hua1,5, YANG Lin2,5, WU Bing-bing2,5, SUN Wei-hua3, LU Wei4, WANG Hui-jun2, CHENG Guo-qiang1, ZHOU Wen-hao2   

  1. 1 Department of Neonatology, Children's Hospital of Fudan University, Shanghai 201102, China; 2 Shanghai Key Laboratory of Birth Defects, The Translational Medicine Center of Children Development and Disease of Fudan University, Children's Hospital of Fudan University, Shanghai 201102, China; 3 The Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai 201102, China; 4 Department of Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University, Shanghai 201102, China; 5 Co-first author
  • Received:2018-12-28 Revised:2019-02-14 Online:2019-02-25 Published:2019-02-25
  • Contact: ZHOU Wen-hao, CHENG Guo-qiang

PDF

1715

Abstract: Objective To compare the diagnostic accuracy of mass spectrometry and high throughput sequencing in screening neonates at high risk of suspected inherited metabolic disorders (IMD). Methods Neonates with suspected IMD were referred to mass spectrometry and next generation sequencing (NGS) with the consent of their guardians from August 2016 to June 2018. Taking NGS (containing 2 742 known pathogenic genes) as the gold standard, the diagnostic value of mass spectrometry (screening diseases including 20 amino acid metabolic diseases, 12 fatty acid metabolic diseases and 19 organic acid diseases) for IMD was discussed. Results Thirty-three of 2 000 neonates with suspected IMD were diagnosed by NGS, including 8 kinds of abnormal organic acid metabolism(15 cases), 7 kinds of abnormal amino acid metabolism(9 cases), 3 kinds of abnormal fatty acid oxidation metabolism(6 cases) and 3 cases of other types of IMD. In these patients, mass spectrometry indicated that there were 128 cases of secondary changes and 26 cases of IMD. When both IMD and secondary changes were considered positive according to the results of mass spectrometry, the sensitivity and specificity of mass spectrometry were 93.9% (95%CI: 79.8%-99.3%) and 93.8% (95%CI:92.6%-94.8%) respectively. In special types of IMD indicated by mass spectrometry, there were 13 cases consistent with NGS, but 2 cases were inconsistent with NGS. Indicated by mass spectrometry, NGS detected pathogenic/likely pathogenic variants of related IMD in 11 cases with several alternatives of IMD, 5 cases with secondary changes and 2 cases with normal results. Five IMDs identified by NGS were not included in the disease spectrum of mass spectrometry in our study. Among the patients with IMD, 12 had family history of suspected IMD. In the 6th month after birth, 13 cases with IMD died of abandoned treatments and 2 cases died of invalid rescue. NGS established therapeutic schemes for 18 infants with IMD. In these patients, 7 developed well and 11 had developmental delay, mainly psychomotor retardation, some of which had hearing impairment. Conclusion Compared with mass spectrometry, the combination of mass spectrometry and NGS can diagnose neonates of suspected IMD more quickly so as to implement individualized treatment as early as possible and improve the prognosis of patients.