第十一届北京罕见病学术大会暨2023京津冀罕见病学术大会征文(019)

1Department of Newborn Screening Center， Beijing Obstetrics and Gynecology Hospital， Capital Medical University， Beijing Maternal and Child Health Care Hospital，

Lulu Li^1#， Yue Tang¹， Jinqi Zhao¹， Nan Yang¹， Lifei Gong¹，

Shunan Wang¹， Haihe Yang¹，Yuanyuan Kong¹*

Background: Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a hereditary metabolic disease. This article reports and discusses the clinical course， biochemical results， and genetic mutation results of four VLCADD patients， clarifying their genetic pathogenic factors and evaluating the application value of genetic diagnosis in the early diagnosis of VLCADD.

Method: This study included four patients， and sample testing was performed for case-2 after the child＇s death. Patients underwent blood tandem mass spectrometry (MS/MS)， urine gas chromatography (GC/MS) and high-throughput sequencing technology. New mutations were analyzed for pathogenicity using SIFT， PolyPhen-2， and Mutation Taster software. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of ACADVL proteins.

Results: A total of four VLCADD patients were diagnosed， including two boys and two girls. All patients showed elevated levels of C14:1， C14:2， and C14. Two of the patients were early-onset neonatal cases， and they died during the neonatal period. Seven mutations were detected among the four VLCADD patients， including four missense mutations: c.218T>C(p.F73S)， c.1292A>G(p.D431G)， c.1349G>A(p.R450H)， and c.553G>A (p.G185S)， one splice-site mutation c.1332+1G>C， one nonsense mutation c.480C>A(p.Y160*)， and one frameshift deletion c.857_865del(p.286_289del). c.218T>C(p.F73S) and c.480C>A(p.Y160*) are novel mutations. The bioinformatics software revealed that the mutations were harmful， and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.

Conclusion:This study identified seven pathogenic mutations in four VLCADD families， including two novel ACADVL gene mutations. These findings contribute to the understanding of the genetic basis and pathogenesis of VLCADD. Meanwhile， this enriches the genetic mutation spectrum and the correlation between genotypes and phenotypes of this disease， indicating that genetic diagnosis plays an important role in the early diagnosis and treatment of VLCADD.