OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

OBJECTIVETo explore the association between metabolic syndrome (MS) and risk of cardiovascular disease events (CVD) in patients with ischemic stroke.

METHODA total of 1087 patients with ischemic stroke were enrolled from 5 community-based medical centres and underwent baseline evaluation on risk factors of stroke during the period of Jan. 2003 to Dec. 2006. After baseline survey, all patients were followed up until Dec 31, 2008 and new CVD events were recorded. MS was defined using CDS criteria. Proportional hazard models were used to assess the HRs and 95% CI of CVD events associated with MS and other components.

RESULTSThe prevalence of MS was 40.4% at baseline. During an average follow-up of 3.5 years, 178 patients developed new CVD events. After adjusted for age, gender, smoking, drinking, marriage status, education level, hospitalization, recurrence of stroke, stroke duration, depression, cognition impairment and ADL, MS remains the independent predictor for the risk of CVD events. Compared with patients with non-MS, the risk of CVD events increased by 44% (HR: 1.44, 95%CI: 1.06 - 1.95). The risk of CVD also increased with the number of MS components. Compared with patients with 1 or less than 1 components of MS, the risk of CVD events increased by 30% (HR: 1.30, 95% CI: 0.83 - 2.04) in those with 2 components and by 69% (HR: 1.69, 95%CI: 1.11 - 2.56) in those with 3 or more components of MS. Hypertension and hyperglycemia and impaired fasting glucose also served as independent risk factors for CVD event (all P < 0.001).

CONCLUSIONSMS was independently associated with increased risk of CVD events in patients with ischemic stroke. There was a dose-response relationship between the numbers of MS components and the risk of CVD event.

Aged ; Brain Ischemia ; complications ; epidemiology ; Cardiovascular Diseases ; complications ; epidemiology ; metabolism ; China ; epidemiology ; Female ; Humans ; Male ; Metabolic Syndrome ; complications ; epidemiology ; Middle Aged ; Prevalence ; Prospective Studies ; Risk Factors ; Stroke ; complications ; epidemiology