Abstract:

Objective To investigate the incidence， clinical manifestations， and gene mutations of short chain acyl-coenzyme A dehydrogenase deficiency （SCADD） in newborns in the Sichuan area. Methods A total of 113，367 neonatal blood samples that were received by the Neonatal Screening Laboratory of Sichuan Provincial Women′s and Children′s Hospital from November 2017 to July 2024， along with 6 outpatient children who had positive re-screening results， were included in this study. Tandem mass spectrometry was employed to detect the level of acylcarnitine in dried blood spots. Neonates with positive primary screening results were recalled within 2 weeks， and further confirmation of SCADD was carried out through urine organic acid analysis， blood biochemistry tests， and gene detection. Results Among 113，367 newborns， 144 children tested positive in the primary screening， 20 were positive in the re-examination， and 7 were diagnosed with SCADD. The prevalence rate was 1/16，195. All 6 outpatient children with positive re-screening results were diagnosed with SCADD， resulting in a total of 13 confirmed cases. All patients showed no clinical symptoms. In 12 cases， blood butyryl-carnitine （C4）， the ratio of C4 to acetyl-carnitine （C2）， and the ratio of C4 to propionyl-carnitine （C3） were increased. In one case， C4 was normal， but the blood valeryl carnitine （C5）， the ratio of C5 to C2， and the ratio of C5 to C3 were increased. Urine organic acid detection revealed an increase in ethyl malonic acid in 8 cases， normal levels in 3 cases， and no detection in 2 cases. Among the 13 confirmed children， 2 were homozygous， and the rest were complex heterozygous. A total of 16 types of ACADS gene mutations were identified， including 15 known mutations and 1 unreported mutation. The known mutations were： c.989G > A， c.1031A > G， c.1165A > G， c.1054G > A， c.655G > A， c.981-983delGAC， c.974G > A， c.983C > A， c.682G > A， c.802C > G， c.46G > A， c.1192C > T， c.293A > G， c.625G > A， c.1195C > T. The unreported mutation was c.796-7C > A. The high-frequency mutation was c.1031A > G （46%）， and there was no significant correlation between the ACADS genotype and the levels of ethylmalonic acid or C4. After the newborns were diagnosed with SCADD， they were provided with dietary guidance， and L-carnitine and vitamin B₂ were supplemented when necessary. During the follow-up period， no clinical symptoms emerged， and their physical and intellectual developments were normal. Conclusions The prevalence of SCADD in the Sichuan region was 1/16，195. A total of 16 mutation sites in the ACADS gene were detected. Children diagnosed with SCADD through neonatal screening exhibited no obvious clinical symptoms and had a good prognosis.

Key words: short Chain acyl-CoA dehydrogenase deficiency, tandem mass spectrometry, gene mutation