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Objective:To study the incidence, clinical features and genetic mutation profiles of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) using screening strategy.Methods:From September 2015 to September 2020, neonates in Xuzhou area were prospectively screened for genetic metabolic diseases using tandem mass spectrometry. Suspected infants were further confirmed using urinary organic acid test and SLC25A13 gene mutation analysis. The clinical manifestations, biochemical and gene mutation results, treatment and prognosis of the confirmed cases were analyzed.Results:A total of 468,494 live-birth newborns were screened with 112 cases suspected and 95 cases received urinary organic acid test and SLC25A13 gene mutation analysis. 13 cases of NICCD were diagnosed with a prevalence of 1/36,038. Most confirmed cases presented with delayed disappearance of neonatal jaundice, feeding difficulties and poor weight gain. Biochemical changes included increased bile acid, abnormal liver enzymes, increased alpha-fetoprotein, hypoglycemia, decreased hemoglobin, abnormal coagulation function and increased blood ammonia. Tandem mass spectrometry showed increased citrulline, methionine, arginine, tyrosine and phenylalanine, and in some cases with slightly increased acylcarnitine. Urine organic acid analysis mainly showed increased 4-hydroxyphenyllactic acid and 4-hydroxyphenylpyruvate. All confirmed cases received genetic mutation tests and a total of 13 mutation loci were detected, including c.852_855delTATG, c.511dupG, c.1638_1660dup, IVS16ins3kb, c.1078C>T, c. 615+5G>A, c.742G>A, c.44G>A, c.1311+1G>A, c.1399C>T, c.889G>T, c.1177+1G>A, c.1841+3_1841+4del, among which, c.852_855delTATG was the most common one. A total of 5 novel mutation loci were discovered in this study with c.1841+3_1841+4del, c.511dupG and c.889G>T predicted as pathogenic variants. Special formula of lactose-free and fortified medium-chain triglyceride (MCT) were used in confirmed cases and most of the symptoms were relieved within 1 year and abnormal indicators significantly improved.Conclusions:The prevalence of NICCD in Xuzhou was 1/36,038. c.852_855delTATG mutation is the most frequent one. Five novel mutation loci are discovered, expanding the SLC25A13 gene mutation spectrum. Most infants with NICCD have a good prognosis, requiring early diagnosis, treatment and life-long follow-up.
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Objective:To study the clinical features and genetic characteristics of isobutyryl-CoA dehydrogenase deficiency (IBDD) of neonates in Xuzhou area.Methods:From October 2016 to October 2021, neonates diagnosed with IBDD using tandem mass spectrometry in Xuzhou area were retrospectively studied. Their clinical phenotypes and genotypes, clinical diagnosis, treatment and follow-up were analyzed.Results:A total of 510 057 neonates were screened and 10 cases of IBDD were diagnosed. The 10 IBDD cases showed increased butyryl carnitine (C4), C4/C2 and C4/C3 during screening and follow-up tests. One case had transient elevated transaminase and one case showed delayed language development. The other 8 cases were otherwise normal. A total of 16 mutation loci of acyl-CoA dehydrogenase 8 (ACAD8) gene were found, including 10 unreported loci: c.567+8C>T, c.213G>T, c.553C>T, c.1190T>C, c.1060G>A, c.494G>A, c.771C>A, c.962A>T, c.715A>G and c.731G>A. Genetic mutations were found in Exon 3, Exon 4, Exon 5, Intron 5, Exon 7, Exon 9 and Exon 10. The hot spots of mutations were c.1176G>T, c. 286G>A and c.1000C>T.Conclusions:IBDD is a rare disease without specific clinical manifestations. Neonatal metabolic disease screening combined with urinary organic acid tests and genetic sequencing can be used for early detection and diagnosis of IBDD. No serious adverse outcome is found in IBDD patients during short-term follow-up, however, long-term follow-up is recommended.
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OBJECTIVE@#To detect pathogenic variant of the FGD1 gene in a boy with Aarskog-Scott syndrome.@*METHODS@#Genetic variant was detected by high-throughput sequencing. Suspected variant was verified by Sanger sequencing. The nature and impact of the candidate variant were predicted by bioinformatic analysis.@*RESULTS@#The child was found to harbor a novel c.1906C>T hemizygous variant of the FGD1 gene, which has led to conversion of Arginine to Tryptophane at codon 636(p.Arg636Trp). The same variant was found in his mother but not father. Based on the American College of Medical Genetics and Genomics guidelines, the c.1906C>T variant of FGD1 gene was predicted to be likely pathogenic(PM1+PM2+PM5+PP2+PP3+PP4).@*CONCLUSION@#The novel c.1906C>T variant of the FGD1 gene may underlay the Aarskog-Scott syndrome in this child. Above finding has enabled diagnosis for the boy.
Subject(s)
Child , Humans , Male , Dwarfism , Face/abnormalities , Genetic Diseases, X-Linked , Genitalia, Male/abnormalities , Guanine Nucleotide Exchange Factors/genetics , Hand Deformities, Congenital/genetics , Heart Defects, Congenital , MutationABSTRACT
1263 children aged 3-6 years old in Wuxi city were included.Overweight 191 children were overweighte,104 obese and 968normal.SPSS analysis showed that deciduous teeth caries and age were positively relative (F=31.77,P=0.0001);obesity and age were not relative(x2 =36.00,P=0.33);deciduous teeth caries and obesity were not relative (F =0.21,P =0.808).Deciduous teeth caries is not related with obesity.
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Objective To explore the clinical significance of serum Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) and D-dimer level detection in children with serious Mycoplasma pneumoniae pneumonia(MPP).Methods Ninety cases of MPP hospitalized children from June 2015 to December 2016 at Affiliated Hospital of Xuzhou Medical College were divided into serious MPP group (42 cases) and mild MPP group (48 cases)according to the severity of their illness.The level of serum D-dimer was detected by immune turbidimetry,and the expressions of TLR4,MyD88 and nuclear factor-κB (NF-κB) were detected by Western blot.Results (1) The level of D-dimer [(1 850.12 ± 153.50) μg/L vs.(297.36 ±27.42) μg/L],white blood counts (WBC) [(11.52 ± 0.38) × 109/L vs.(7.98 ± 0.62) × 109/L],neutrophile granuloeyte ratio (N) (0.87 ± 0.01 vs.0.55 ± 0.01),C-reactive protein (CRP) [(64.59 ± 7.93) mg/L vs.(19.79 ± 6.38) mg/L],as well as erythrocyte sedimentation rate (ESR) [(52.13 ± 1.8) mm/1 h vs.(22.78 ± 1.43) mm/1 h] in the serious MPP group were higher than those in the mild MPP group,and the differences were statistically significant (t =6.511,3.342,2.891,8.075,7.922,all P ＜ 0.05).(2)The expression of TLR4 (1.53 ±0.12 vs.0.45 ± 0.07),MyD88 (1.28 ±0.10 vs.0.37 ±0.12) and NF-κB (1.49 ± 0.16 vs.0.53 ±0.10) in the serious MPP group were higher than those in the mild MPP group,and the differences were statistically significant (t =3.511,7.614,8.122,all P ＜0.05).(3) The D-dimer levels,TLR4,MyD88 and NF-κB of the cases who had the image feature of lung patchy shadow (46 cases),atelectasis (17 cases) and pleural effusion (29 cases),were obviously higher than those who had not,and the differences were statistically significant(all P ＜ 0.05).(4) The plasma D-dimer level [(2 984.19 ± 138.43) μg/L vs.(640.48 ± 78.89) μg/L]and expressions of TLR4(2.53 ± 0.41 vs.0.92 ± 0.17),MyD88 (2.18 ± 0.12 vs.0.57 ± 0.06),NF-κB (2.47 ± 0.16 vs.0.89 ± 0.15) in the cases with extrapulmonary complications (13 cases) were higher than those without extrapulmonary complications,and the differences were statistically significant (all P ＜ 0.01).Conclusion The expression of TLR4/MyD88 increased in consistent with the up-regulation of D-dimer level in children with serious MPP,which indicated that the TLR4/MyD88 signaling pathway may participate in the formation of hypercoagulable state of children with serious MPP.
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<p><b>OBJECTIVE</b>To explore prenatal related factors of high BMI status in children at 1 and 2 years of age.</p><p><b>METHOD</b>A total of 2 220 newborns from Shenyang, Wuhan and Guangzhou were recruited in this birth cohort, thereafter they were followed up to two years of age.Self-administered questionnaires were used to collect such variables as social-demographic characteristics and feeding practice, etc. The anthropometric measures of children were collected by trained health staff. The data were subjected to multiple logistic regression analysis to determine the related factors for high BMI among infants and toddlers.</p><p><b>RESULT</b>The number of children with high BMI status were 550 (32.80%) at one year of age and 309 (26.23%) at two, respectively. The number of boys with high BMI status were 178 and girls 309 at age two years. The prevalence of high BMI status among boys (29.1%) at age two was significantly higher than that of girls (23.1%) (χ² = 5.52, P = 0.02). Logistic regression analysis showed that after the adjustment for sex, parental educational level, family economic status and other confounding factors, maternal passive smoking during pregnancy [OR:aged one:1.38 (1.05-1.82);aged two:1.48 (1.05-2.09)], maternal pre-pregnancy overweight and obesity [aged one:1.29 (1.05-1.58); aged two:1.35 (1.04-1.76)], paternal overweight and obesity [aged one:1.50 (1.21-1.87); aged two:1.47 (1.11-1.95)] and birth weight [aged one:1.53 (1.05-1.82); aged two:1.87 (1.33-2.63)]were identified to be associated with high BMI status in children.</p><p><b>CONCLUSION</b>Maternal passive smoking during pregnancy, paternal and maternal (pre-pregnancy) overweight or obesity and high birth weight are found to be important related factors for high BMI status in young children. Childhood overweight/obesity prevention should be considered starting as early as before pregnancy.</p>