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

Objective To compare and explore the differences of clinical characteristics between human adenovirus type 7 (HAdV7) and type 55 (HAdV55) infections in adults,and to provide evidences for clinical management.Methods The data of clinical manifestations,laboratory examinations,chest computed tomography and prognosis of 214 cases with HAdV7 and 235 cases with HAdV55 infections from 2012 to 2018 were retrospectively collected and analyzed.The chi-square test was used for the categorical variables,and the rank sum test was used for the continuous variables of non-normal distribution.Results Compared with patients in HAdV55,those in HAdV7 group displayed more diarrhea (12.1％ [26/214] vs 2.6％ [6/235],x2 =15.583),more laryngeal lymphatic follicles (33.2％ [71/214] vs 17.9％ [42/235],x2 =23.566),more tonsil enlargement (56.5％ [121/214] vs 20.0％ [47/235],x2 =63.870) with secretions (33.2％ [71/214] vs 11.5％ [27/235],x2 =30.878),more leukocytosis (24.8％ [53/214] vs 14.0％ [33/235],x2 =8.318),more monocytosis (78.0％ [167/214] vs 52.8％ [124/235],x2 =31.364),more thrombocytosis (7.1％ [15/212] vs 3.8％ [9/235],x2 =5.835),more elevated level of C-reactive protein (80.8％ [97/120] vs 64.3％ [137/213],x2 =10.020),more abnormalities of liver function (alamne aminotransferase [ALT]:13.5％ [28/207] vs 5.6％ [13/232],x2 =8.111) and myocardial enzymes (creatine kinase [CK]:37.6％ [77/205] vs 26.4％ [61/231],x2 =6.246),creatine kinase isoenzymes ([CK-MB]:35.6％ [73/205] vs 11.1％ [24/216],x2 =35.600),and all the differences were statistically significant (all P ＜ 0.05,0.01).Compared with patients in HAdV7 group,those in HAdV55 group displayed longer duration of diseases (7 [5]days vs 6[5] days,Z=-2.632),more sore throat (72.8％ [171/235] vs 62.1％ [133/214],x2 =0.016),more headache (62.1％ [146/235] vs 16.4％ [35/214],x2 =97.527),more pharyngeal congestion (93.6％ [220/235]vs 74.8％ [160/214],x2 =30.602),more leukopenia (14.0％ [33/235] vs 24.8％ [53/214],x2 =8.318),and more elevated level of lactate dehydrogenase (12.6％ [29/230] vs 6.3％ [13/205],x2 =4.881),more pneumonia (71.5％ [168/235] vs31.8％ [68/214],x2 =70.846) (all P＜0.05,0.01).Conclusions The clinical characteristics of HAdV7 and HAdV55 infections in adults are different.The type 55 infection is more likely to develop to pneumonia,while the type 7 infection has wider tissue tropism.

Objective To investigate the role and mechanism of resveratrol in a rat model of complex region-al pain syndrome type Ⅰ(CRPS1). Methods 50 male SD rats were divided into control group(group A),sham operation group(group B),model group 1(group C),model group 2(group D),and model group 3(group E). Groups A,B and C received 5%DMSO;group D received ISO-1 of 1 mg/(kg·d);and group E received resveratrol of 20 mg/(kg · d)for 14 days. Pain behaviors were assessed on days 0,7,and 14. Serum levels of MIF and TNF-αwere detected by ELISA. MIF ,total ERK1/2 and p-ERK1/2 in sciatic nerve were detected by Western blot. Re-sults On days 7 and 14 after treatment,resveratrol injection,similar to ISO-1,significantly improved the pain threshold;serum levels of MIF and TNF-α were significantly decreased;expressions of MIF ,total ERK1/2 and p-ERK1/2 in sciatic nerve were also decreased significantly in group E,which were significantly lower than group C (P < 0.05). Conclusions Resveratrol can significantly improve pain threshold ,decrease expressions of MIF and p-ERK1/2 in a rat model of CRPS1,which might be involved in the inhibition of ERK signaling pathway.