Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7‐year study in eastern coastal areas of China

Abstract

Background The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area. Methods The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis. Results Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was—IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short‐chain acyl‐CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were—PAH gene for PKU: c.728G > A, c.442‐1G > A, c.611A > G, c.721C > T; PTS gene for non‐classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del. Conclusion This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM.

Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey

“…However, if we include the five IMD conditions beyond the scope of our NBS program and the six parental conditions we diagnosed, the PPV would be 19.7%. This PPV figure is similar to that of Singapore [17] (20%) and Germany [18] (11.3%), is much higher than that reported by eastern China [19] (1.7%) and Malaysia [10] (3.17%) and is lower than that reported by Spain [11] (24.6%), Norway [20] (41.2%), and Sweden [13] (47%). This discrepancy is likely due to the fact that the NBS program in Hong Kong and other Asian countries is relatively new compared to countries such as Norway and Sweden, who started using NBS TMS in 2012 and 2005, respectively.…”

“…However, this incidence was much higher than our other Asian counterparts’ reports, such as Japan (1 in 30,000) and Taiwan (1 in 34,000) [ 21 ]. Yunus et al [ 10 ] in Malaysia also did not detect any FAOD in babies undergoing NBS and those who underwent high-risk screening of IMD, whereas China, as reported by both Men et al and Deng et al [ 9 , 19 ], had a midway incidence of FAOD between 1 in 10,917 to 1 in 11,145. Although Singapore reported an incidence of FAOD similar to Hong Kong (1 in 6330) [ 17 ], it may not be comparable to Hong Kong since the most common FAOD in Singapore is short-chain acyl coA dehydrogenase (SCAD) deficiency, which is not part of the Hong Kong NBS panel.…”

Integrating Newborn Genetic Screening with Traditional Screening to Improve Newborn Screening

“…The combination of MS/MS and NGS (MS/MS-NGS) is an enhancement program for NBS. Currently, an increasing number of countries are using MS/MS-NGS as the main method for NBS and have achieved positive outcomes [30,37,38]. The primary objective of NBS is to identify only treatable diseases and those that have a signi cant impact on the cost of quality of life through early detection.…”

“…Dried blood spots were collected from all newborns 72 h after birth on lter papers (903, Hangzhou Matridx Biotechnology Co., Ltd.). MS/MS-NGS: MS/MS was used to detect the biochemical indicators, and newborns were further investigated to diagnose the diseases by NGS (panel), as described in our previous study [30]. Newborn diseases detected by MS/MS-NGS included 56 common IEM with 86 genes (Supplementary Table S1).…”

“…A targeted gene panel is used in the genetic screening of newborns [29,14], which can be designed "as required" to incorporate disease-related genes of interest. Targeted gene panels are now being incorporated into routine genetic screening in a growing number of countries and regions around the world, and diverse genes can be included in the targeted gene panels [17,18,21,30], but these panels play a role in diagnosis after MS/MS screening. How to use a panel as a genetic screening program for newborns in clinical practice still needs to be explored.…”