OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. METHODS: A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords "RELA" "NF-κB" "autoinflammatory disease" "tofacitinib" "sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. CONCLUSION The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.
Humans ; Male ; Transcription Factor RelA/genetics* ; Female ; Hereditary Autoinflammatory Diseases/genetics* ; Child ; Pedigree ; Exome Sequencing

Objective:To explore the values of fat saturation sequence in MRI for juvenile arthritis.Methods:A total of 1 131 cases with juvenile arthritis and 1 601 with symptomatic arthritis were examined by MRI normal T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI)sequence and spectral presaturation attenuatedinversion recovery (SPAIR) T2 fat saturation sequence.All the images were independently evaluated by two senior doctors from the Department of Radiology and the Department of Pediatric Rheumatology and Immunology respectively to confirm the types and degree of pathological changes of joint tissues.Results:Among the subjects,847 patients demonstrated positive in MRI,accounting for 52.9％;409 patients showed positive in normal sequence,accounting for 48.3％;816 patients showed positive in fat saturation sequence,accounting for 96.3％.Joint hydrops accounted for 59.5％.Bone marrow edema accounted for 39.7％.The relevant ratio of bone marrow edema,joint hydrops,thickening of synovium and cartilage injuries in fat saturation sequence were higher than that in normal sequence (P＜0.05).The relevant ratio of bone erosion in normal sequence was higher than that in fat saturation sequence (P＜0.05).However,no significant difference of joint cysts was found between the fat saturation sequence and normal sequence (P＜0.05).Conclusion:Application of fat saturation sequence by MRI to check juvenile arthritis could obviously improve the positive MRI relevant ratio.In addition,the relevant ratio of the early pathological changes of juvenile arthritis (such as bone marrow edema and joint hydrops) was high,which might provide references for the early diagnosis of juvenile arthritis.

Objective To explore the correlation between the distribution of uric acid (UA) level and the biochemical indicators which reflect the degree of organ lesions among hospitalized children.Methods Patients who were hospitalized to the Department of Pediatrics and received the blood UA test from June 2012 to October 2013 were included,23 217 cases in total.The biochemical analyzer-Japan's Olympus AU 2700 was used to detect blood biochemistry; and uricase-peroxidase coupling method was used to detect blood UA.Among these patients,2 099 cases whose UA level exceeded the normal level.Then the patients' gender,age,primary diagnosis and UA level were recorded; and the distribution of their UA level was described.The Chi-square or Fisher test was used to assess the incidence rate.At the same time,each blood biochemical indicators of the patients with high UA level were recorded ; and the relationships between the blood UA of the 1 650 patients with complete records and each blood biochemical indicator were analyzed with Pearson correlation analysis.Results The incidence rate of hyperuricemia among the hospitalized children was 9.04％(2 099/23 217).In particular,the incidence rate among boys and girls was 6.5t％(890/13 657) and 12.65％ (1 209/9 560) respectively (x2 =256.9,P＜0.05).The incidence rate of hyperuricemiin different diseases was as follows:in the critical illness 36.93％ (113/306),neonatal disease 20.34％ (922/4 533),urinary system diseases 12.08％ (47/389),circulatory system diseases 11.67％ (21/180),nervous system diseases 11.05％(112/1 014),digestive diseases 10.50％(190/1 810),infectious diseases 10.18％(120/1 179),blood diseases 7.58％ (55/726),endocrine system diseases 5.74％ (17/296),autoimmune diseases 4.24％ (48/1 131),respiratory diseases 3.90％ (454/11 653) respectively (x2=1423.0,P＜0.05).The incidence of hyperuricemia at younger than one month was 18.31％(929/5 075),younger than one year old was 4.22％ (359/8 501),younger than six years old was 10.68％(600/5 618),younger than 15 years old was 5.24％ (211/4 023) respectively (x2=858.5,P＜0.05).Blood UA was positively correlated to urea nitrogen,creatinine,lacticdehydrogenase,α-hydroxy-butyrate dehydrogenase,creatine kinase and creatine kinase-MB (r=0.426,0.44,0.324,0.367,0.413,0.431,P＜0.05).Blood UA was not correlated to fructosamine,blood glucose,triglycerides,total cholesterol,low-density lipoprotein and high density lipoprotein.Conclusion The incidence of hyper-uricemia among hospitalized children is high; and the incidence among children with severe diseases and newborn babies is high; followed by in children with urinary system and circulatory system diseases.The blood UA level is closely related to the blood biochemical indicators which reflect the lesions of heart and kidney.

Objective To observe the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP),high density lipoprotein cholesterol (HDL-C) in predicting cardiovascular damage in Kawasaki disease (KD).Methods Enzyme-linked fluorescence analysis (ELFA) technique was used to measure serum NT-proBNP levels in 406 KD patients [including 104 cases of incomplete Kawasaki disease (IKD)] at the acute phase,the convalescent stage,at the same time,the blood HDL-C,Albumin,globulin,alanine aminotransferase (ALT),C-reactive protein (CRP),red blood cell sedimentation rate (ESR),blood white cell count (WBC),hemoglobin (Hb),blood platelet count (PLT) level were tested.According to the results of echocardiography,electrocardiogram,myocardial enzymes in KD,patients were divided into two groups:two hundred and twenty-two with cardiovascular damage and 184 without cardiovascular damage group.The age,gender,fever,the first application of the intravenous gamma globulin,laboratory markers of clinical features observed above the detection levels were compared,and these parameters for each group were compared using t test or analysis of variance,the single factor which was statistically significant were received operating characteristic curve (ROC) analysis.Then the cardiovascular damage group was divided into echocardiography abnormal group and echocardiography normal group,and t test was adopted to compare the clinical parameters of the two groups.Results ① The age,lip and oral changes,the first application of intravenous gamma globulin,blood NT-proBNP,HDL-C,albumn and ALT was significantly different between the cardiovascular damage group and non cardiovascular damage group (t/x22=4.989,4.721,6.212,18.834,12.788,4.851,4.541,All P＜0.05).② When the blood NT-pro-BNP was higher than 786.5 ng/L,its sensitivity and specificity for differentiating KD with cardiovascular damage was 86.5％ and 84.8％,respectively.When the blood HDL-C was lower than 0.655 mmol/L,its sensitivity and specificity for differentiating KD with cardiovascular damage was 80.4％ and 69.4％ respectively.When the blood NT-proBNP was higher than 786.5 ng/L in addition to HDL-C lower than 0.655 mmol/L,the specificity for differentiating KD with cardiovascular damage was 91.8％.③ For the 222 cases with cardiovascular dam-age,their blood NT-proBNP,HDL-C levels were statistically significantly different between the echocardiogra-phy abnormal group and echocardiography normal group (t=3.354,4.084,All P＜0.05).④ The serum NT-proBNP,ALT levels of the 406 acute and convalescent KD patients were significantly higher than the recovery phase.The blood HDL-C,albumin level of acute patients were significantly lower than those at the recovery phase,the difference was statistically significant (t=22.335,4.951,20.334,15.073,All P＜0.05).⑤ One hundred and four children with IKD were divided into patients with cardiovascular damage (74 cases) and without cardiovascu-lar damage (30 cases),the age,lip and oral changes,the first application of intravenous gamma globulin,blood NT-proBNP,HDL-C,albumin and ALT were significantly differentbetween these two groups (t=3.083,2.157,6.423,6.409,3.649,8.658,All P＜0.05).Conclusion Blood NT-proBNP and HDL-C are good pre-dictive parameters in children with cardiovascular damage of KD,IKD.