Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

Objective:To analyze the variation and characteristics of gene mutation in patients with 6-pyruvoyltetrahydropterin synthase deficiency(PTPSD) in Henan province, and to provide the theoretical basis for early diagnosis, treatment, genetic consultation and prenatal diagnosis of PTPSD.Methods:One thousand nine hundred and six children with hyperphenylalaninemia (HPA) treated in Henan Neonatal Screening Center, the Third Affiliated Hospital of Zhengzhou University from January 1998 to December 2018 were included.Chemiluminescence was used for pheny-lalanine (Phe) detection in blood or dried blood spots.For patients with Phe concentration >120 μmol/L, urine pterin analysis was carried out, and the activity of dihydropteridine reductase (DHPR) was detected.Mutations of the PAH, GCH1, GFRP, PCBD1, PTPS and QDPR in 79 children with tetrahydrobiopterin deficiency(BH4D) were detected by using the high-throughput sequencing.All variations were verified by Sanger sequencing. Results:Among the 1 906 children, 79 cases were diagnosed as BH4D clinically, and they all were PTPSD.The incidence of PTPSD in HPA in Henan was 4.14%.One hundred and fifty-six out of 158 alleles in 79 children were detected, and the detection rate of gene mutation was 98.73%, 30 mutations were identified and most of the variants were located in exons 5(92/156 cases, 58.97%). Variants of c. 259C>T (61/156 cases, 39.10%), c.286G>A (17/156 cases, 10.90%), c.155A>G (13/156 cases, 8.33%) and c. 272A > G (10/156 cases, 6.41%) were more common.Six novel variations were detected, which included c. -77G>T, c.158A>G, c.262C>T, c.207G>A, c.316A>G and c. 332C>G; 38 genotypes had been identified, including 3 homozygous mutations and 33 compound heterozygous mutations.Conclusions:c. 259C>T is the hot-spots gene mutation in Chinese PTPSD patients in Henan province.The identification of 6 new mutations enriches the gene mutation profile.

Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.