A retrospective analysis of MS/MS screening for IEM in high-risk areas

Abstract

Inborn errors of metabolism (IEM) can lead to severe motor and neurological developmental disorders and even disability and death in children due to untimely treatment. In this study, we used tandem mass spectrometry (MS/MS) for primary screening and recall of those with positive primary screening for rescreening. Further diagnosis was based on biochemical tests, imaging and clinical presentation as well as accurate genetic testing using multi-gene panel with high-throughput sequencing of 130 IEM-related genes. The screening population was 16,207 newborns born between July 1, 2019, and December 31, 2021. Based on the results, 8 newborns were diagnosed with IEM, constituting a detection rate of 1:2,026. Phenylketonuria was the most common form of IEM. In addition, seven genes associated with IEM were detected in these eight patients. All eight patients received standardized treatment starting in the neonatal period, and the follow-up results showed good growth and development. Therefore, our study suggests that MS/MS rescreening for IEM pathogenic variants in high-risk areas, combined with a sequencing validation strategy, can be highly effective in the early detection of affected children. This strategy, combined with early intervention, can be effective in preventing neonatal morbidity and improving population quality.

Keywords: Genetic testing; Inborn errors of metabolism; Newborn screening; Sequencing; Tandem mass spectrometry.

Fig. 1

Flow chart of IEM screening and the diagnosis process

Fig. 2

Characteristics of cranial MRI in a patient with methylmalonic acidemia (A, B) and a patient with glutaric acidemia (C, D). A: Iso-T1 and long T2 signals shown in the white matter of the frontal lobes, bilateral frontal white matter demyelination enhancement and mild dilatation of the lateral ventricles (at 3 months of age). B: Normal (at 2 years of age). C: The bilateral temporal subarachnoid space was significantly enlarged (at 3 months of age). D: Normal (at 2.5 years of age)