Objective To analyze the relationship between 25 hydroxyvitamin D and attention deficit and hyperactivity disorder by Meta-analysis. Methods Pubmed, EMbase, Cochrane Library, Wanfang and CNKI database were searched up to March 2018, references related to vitamin D and ADHD were retrieved and collected. Using the Newcastle - Ottawa scale for quality assessment, a meta-analysis was performed by RevMan 5.3 statistical software. Results 14 articles were included in this study. 9 case-control studies which included 2709 cases in ADEM group and 12024 cases in control group were analyzed by Meta-analysis. The results shows that the serum 25(OH)D levels were found to be significant lower in the ADHD group compared to health controls (WMD=-6.03, 95%CI: -8.26~-3.79). 5 prospective cohort studies related to the vitamin D levels of pregnant mother / cord blood and ADHD showed that higher serum concentrations of 25(OH)D3 in the 13 weeks of pregnant significantly decrease the risk of ADHD in offspring, and the relationship between 25(OH)D3 levels of 30 weeks of pregnant/cord blood and ADHD was not clear. Conclusion The higher serum 25(OH)D3 levels of early pregnancy and children were decrease the risk of ADHD.
ObjectiveTo systematically review the association between high fat diet (HFD) and asthma or recurrent wheezing in children. MethodsThe inclusion participants were from communities, schools or medical institutions with the exposure factor of the high fat diet(HFD). Observational studies (cross-sectional and cohort studies) assessing the outcome of asthma or recurrent wheezing were included. The databases of PubMed, Embase, Clinical trials, Central, Web of Science, VIP, Wanfang Data and CNKI up to April 1, 2018 were searched for the relevant studies. Two authors performed the literature screening, data extraction and methodological quality evaluation. Using the Newcastle-Ottawa Scale (NOS) for cohort study and Agency for Healthcare Research and Quality(AHRQ) for cross-sectional study. The meta-analysis was conducted by the Stata 12.0 software. ResultsThe final 12 observational studies with 17 622 participants, ranging from 3 to 17 years old, were included. The included studies contained 9 cross-sectional studies (5 articles in 8 points, 3 articles in 7 points and 1 article in 6 points with AHRQ) and 3 cohort studies (2 articles in 8 points and 1 article in 7 points with NOS). ①The risk of pediatric asthma with HFD was significantly 78% higher than non-HFD (OR=1.78, 95%CI: 1.44-2.21, P＜0.001, adjusted by sensitivity analysis). Pediatric asthma had a significant association with the dietary pattern of western diet (OR=1.79, 95%CI: 1.28-2.51), and with the individual high-fat foods(OR=1.86, 95%CI: 1.26-2.68).②The risk of recurrent wheezing with HFD in children was significantly 33% higher than non-HFD (OR=1.33, 95%CI: 1.16~1.51, P＜0.001, adjusted by sensitivity analysis). The test of publication bias using Egger's regression method showed the absence of publication bias in included studies. ConclusionThe HFD was significantly associated with asthma and recurrent wheezing in children.
Objective To study the safety of arsenic using in children with acute promyelocytic leukemia(APL). Methods Fifteen children with APL diagnosed in our hospital from March 16, 2016 to May 1, 2018 were enrolled. The arsenic concentrations in different tissues including blood, urine, hair and nail, were measured during different treatment timepoints, and adverse reactions were observed to evaluate the safety of arsenic using in children with APL. Results All blood arsenic concentrations in children with CCLG-APL 2016 protocol were within the effective range of (10-100) ng·mL-1 during induction, consolidation and maintenance therapy, except for two cases were 121.3 ng·mL-1 and 9.46 ng·mL-1 during consolidation, respectively. After six months of discontinuation, the arsenic concentrations of blood and urine, with a level of 1.7 ng·mL-1 and 40.4 ng·mL-1, were reduced to normal levels as those before treatment, between which there was no significant difference (P>0.05). Arsenic concentrations in hair and nail peaked at the time of drug withdrawal and gradually decreased to the level before treatment after six months of discontinuation. In addition, it showed that blood arsenic concentration was positively correlated with urine (r=0.778, P<0.001), hair (r=0.641, P<0.001) and nail (r=0.655, P<0.001) arsenic. Arsenic concentration in urine with hair (r=0.622, P<0.001), and nail (r=0.688, P<0.001) were also positively correlated. And arsenic concentration in hair was positively correlated with nail (r=0.847, P<0.001). Up to now, with a longest follow-up period of 25.5 months and the average follow-up time of (12.2±7.8) months, the short-term response of arsenic disappeared after symptomatic therapy or arsenic reduction, and no chronic side effects of arsenic were observed. Conclusion Through the detection of arsenic concentration in different periods and different tissues, it was found that the blood arsenic concentration could be maintained within the effective concentration range in each treatment stage, and the arsenic concentration in blood, urine, hair and nails gradually decreased to normal after six months of discontinuation. The use of arsenic in children with APL is safe, but it still needs long-term follow-up.
Objective To investigate the composition of nosocomial infection sites and pathogens changes in hospitalized children in a children's hospital and provide scientific basis for prevention and control of nosocomial infections. Methods Hospitalized children diagnosed with nosocomial infection from January 1, 2012 to December 31, 2017 were selected as the study subjects. Specimens were collected for pathogen detection. The composition of nosocomial infection sites and pathogens changes were analyzed, comparing 2012-2014 with 2015-2017. Results The total number of children diagnosed with nosocomial infection was 1 991 and the number of nosocomial infections was 2 022. There were 1 212(60.9%) boys, and the age of the children was 2.0(0.6,5.0) years(1 d to 17 years). There were no significant differences in gender and seasons in children with nosocomial infection between 2012-2014 with 2015-2017 (P was 0.618 and 0.145, respectively), while the difference in age distribution was statistically significant (P< 0.001). ①The top four infection sites were lower respiratory tract (28.8%), gastrointestinal tract (25.7%), upper respiratory tract (25.2%) and bloodstream infection (10.4%). Comparing 2012-2014 with 2015-2017, the compositions of lower respiratory tract and bloodstream infections were significantly increased (P=0.016 and 0012, respectively). The most frequent sites of nosocomial infection were bloodstream infection in Neonatal Department(49.1%), lower respiratory tract infection in PICU (69.6%), respiratory infection in general wards (58.7%), while infection rate in the central nervous system, urinary tract, and surgical site in Department of Pediatric Surgery was higher than those in Neonatal Department, PICU and general wards. ②The rate of microbiological examination was 81.8%(1 655/2 022), and the positive rate was 49.3%(821/1 667). The most frequent pathogens detected were gram-negative bacteria (39.4%) and virus (34.8%), followed by gram-positive bacteria (17.9%) and fungi (6.9%). Comparing 2012-2014 with 2015-2017, the composition of gram-negative bacteria was decreased (45.2% vs 34.6%, P=0.002), while that of gram-positive bacteria was increased (13.8% vs 213%, P=0.005). Klebsiella pneumoniae was the top pathogen to be detected(14.0%), which mainly caused the hospital's lower respiratory tract (44.0%) and bloodstream (44.0%) infections. Acinetobacter baumannii ranked the second (13.4%), and up to 75% of the strains caused lower respiratory tract infections. In addition, about 2/3 of enterococci caused bloodstream infections. Gastrointestinal infections were mainly caused by rotavirus-infected diarrhea. Conclusion The composition of nosocomial infection sites in different departments is different. PICU and Neonatal Department need to pay attention to hospital-acquired pneumonia and bloodstream infections. Invasive operations should be reduced or avoided and the antimicrobial drugs should be used rationally to minimize the occurrence and spread of drug-resistant bacteria.
Objective A patient with fructose intolerance (HFI) with ALDOB compound heterozygous mutations was identified, and the follow-up data for 30 years was summarized. Methods The clinical manifestation and the experience of diet control were retrospectively summarized, and the gene sequencing results and the long-term outcome were also reported. The recipes that could cause HFI symptoms in the patient were systematically selected and recorded. The clinical information of patients with the known pathogenic mutations of ALDOB gene in HGMD was collected through literature review, the potential relationship between diet control and follow-up outcome was analyzed in patients with detailed clinical information. Results A 4-year-old girl suffered from fever due to unknown reasons, and the symptoms were relieved after vomiting. From the 20th day after birth, vomiting was observed immediately after the milk feeding. After changing to rice porridge, vomiting symptom was alleviated. In the childhood, due to the observation that the patient would vomit after eating foods like watermelon and cakes, the intake of sugary foods was avoided. At the age of 7 years, the patient was diagnosed as "developmental delay, inherited metabolic disorder？" with the chief complaints of low-fever, hunger after eating sweet foods and vomiting could relieve the symptoms. Meanwhile, parents started to select and record fruits, vegetables and other foods that could cause vomiting. The patient was followed up to 30 years old, with the height of 174.6 cm, the weight of 57.6 kg, normal intellectual development. No abnormalities were observed in heart, lung, thyroid, liver and kidney functions. The patient summarized detailed dietary contraindications and expected to perform genetic testing to identify the inherited metabolic diseases for diagnosis. The patient was tested by whole genome sequencing and Sanger validation and it turned out that she carried compound heterozygous mutations of ALDOB gene ［NM_000035, exon4:c.360_363delCAAA(p.N120Kfs*32); exon9:c.1013C>T (p.A338V)］. A338V was inherited from her father and N120Kfs*32 from her mother. In this article, 33 known pathogenic mutations of ALDOB gene reported by HGMD with detailed clinical information were collected. Six of the 8 (75%) patients without diet control had poorer prognosis than those with diet control (9/18, 50%). Among the diet-controlled patients, 55.6% patients of poor prognosis were with frameshift mutations, higher than the percentage of patients with good prognosis (27.8%). Conclusion Diet control is important for improving prognosis. However, there is a risk of poor prognosis for patients with frameshift variants even with well diet control, which need stricter diet control and close follow-up.
Objective To compare the detection results of the copy number variations analysis pipeline based on high-throughput sequencing (PICNIC) and conventional array comparative genomic hybridization. Methods We enrolled patients underwent both aCGH detection and high-throughput sequencing in Children's Hospital of Fudan University from January 1, 2016 to December 31, 2017. Informed consent was obtained from the parents. We have established an operational pipeline (PICNIC) which detect, annotate and prioritize CNVs from raw high-throughput sequencing data combined with clinical information for disease diagnosis. The CNVs identification between aCGH platform and the PICNIC pipeline were compared to prove the utility value of PICNIC. The aCGH platform used the Agilent's SurePrint 180K Kit for experiment and specific softwares for data processing and copy number variation identification. Detected CNVs with duplications >500 kb and deletions >200 kb were remained for further analysis. With the manually evaluation of the patient's clinical phenotypes and the CNV's function, Pathogenic/Likely-pathogenic (P/LP) were concluded for the CNVs that reported phenotypes were in accordance with the patients phenotypes while Variants of Unknown Significance (VUS) for the not exactly matched ones. The PICNIC analysis pipeline started with the BAM file generated from the sequencing data. After the exon coverage depth calculation and the quality control, CANOES was used for the CNVs detection. The detected CNVs were further annotated and filtered for both gene level and regional level. The detection rate and sensitivity of these two methods were compared.In this study, we performed aCGH and PICNIC on 113 samples and compared the result of CNVs detection between these two methods. Results Altogether, 113 cases underwent both aCGH detection and PICNIC analysis were enrolled, with an average age of 2 years old. The patients including 82 developmental delay cases, 16 seizures cases, 5 autism cases, 3 congenital heart disease cases and 7 genetic counseling cases. The aCGH test detected 76 P/LP CNVs and 16 VUS CNVs while PICNIC detected 92 P/LP CNVs and 21 VUS CNVs. All of the P/LP and VUS CNVs detected by aCGH were consistently detected by PICNIC and 16 VUS CNVs detected by aCGH were concluded as P/LP by PICNIC. Taking aCGH as the gold standard, the detection of PICNIC showed that sensitivity was 100% (95% CI: 94%-100%), specificity was 100% (95% CI: 81%-100%), positive predictive value was 82.6% (95% CI: 73%-89%), and negative predictive value was 56.8% (95% CI :40%-72%). Among the 446 aCGH detected CNVs, PICNIC verified 190 of them; among the 236 CNVs detected by PICNIC, aCGH identified 190 of them. Conclusion The CNVs analysis pipeline based on high throughput sequencing (PICNIC) demonstrated 100% specific and sensitive to Pathogenic/Likely pathogenic CNVs, and could be used in clinical detection. The establishment of this method and its clinical popularization were of great significance for further high-throughput capture sequencing data mining and re-analyzing.
Objective To investigate the clinical and genetic features of epileptic encephalopathy caused by STXBP1 mutations. Methods The patients with epileptic encephalopathy caused by STXBP1 mutations were recruited from December 30, 2011 to January 31, 2018 in our hospital, and their gene data and clinical data including treatment and outcome were analyzed. Results There were 8 children (4 females and 4 males) in this study. The onset age ranged from 2 d after birth to 6 months, and the mean age was 15 days. All the patients had moderate to severe development delay, poor reaction and eye chasing. Two patients had opisthotonos, and 1 patient was observed with dark skin especially on the scrotum. The EEG abnormalities were burst-suppression pattern in 4 cases and hypsarrhythmia in 3 cases, and multifocal discharges on both side in 1 case. DST was checked on 2 patients. DQ<50 and MI<50 in both of them. One patient had laryngomalacia and adrenal glands enlargement. One male was clinical diagnosed with ASD. Seven mutation sites were detected: 5 missense mutations, 1 deletion mutation，and 2 nonsense mutations. Mutations of c.1216C>T (p.R406C)，c.246G>A(p.K82K), c.1702G>A(p.G568S) and c.54delG were novel and were predicted as harmful. The mutations of c.1439C>T(p.P480L)， c.585 C>G(p.Y195X) and c.1162C>T(p.R388X) were recorded in Human Gene Mutation Datebase (HGMD). Four cases were diagnosed with Ohtahara syndrome and 3 were WEST syndrome, while the initial phenotype of 1 patient did not fit into a specific recognized epilepsy syndrome. Seizures were well controlled with AEDs in 5 cases with 1 or 2 combined anti-epilepsy medicine. Three patients were refractory. Conclusion STXBP1-related epileptic encephalopathy is a severe neurological disorder. Adrenal glands enlargement may be a new phenotype associated with epileptic encephalopathy.
Objective To explore the genotype and clinical characteristics of the leukoencephalopathy with thalamus and brainstem involvement and high lactste (LTBL) caused by the mutation of EARS2 gene, and to improve the understanding of the disease. Methods The clinical characteristics, laboratory examination and genetic testing of one case of LTBL were presented，analyzed and discussed. The related literatures were reviewed. Results The male case presented jaundice from the second day after birth. Liver failure (severe cholestasis, hypoglycemia and dysfunction of blood coagulation), typical LTBL clinical features including severe lactic acidosis, growth and mental retarration besides hypoglycemia were found after the age of 42 days. Brain MR revealed multiple brain injury. Genetic sequencing from the child and his parents revealed compound heterozygous variants in EARS2 gene: c.1355T>G（p.L452R）and c.813C>A（p.F271L）. At the age of 15 months old, biochemical markers (including liver enzymes, bilirubin, blood glucose and lactic acid ) were completely normal and delayed psychomotor development was obvious. Brain MR showed severe hydrocephalus. Hydrocephalus and delyed motor development improved greatly after 6 months of ventriculo-peritoneal drainage. Conclusion Liver failure is one of the early major manifestations of LTBL caused by gene mutation in EARS2. With age, hydrocephalus may be one of the clinical features of this disease. EARS2 gene mutations of c.1355T>G (p.L452R) and c.813C>A (p.F271L) are the pathogenic gene mutations of LTBL. The clinical features and genotypes of LTBL should be further studied.
ObjectiveTo report a case of childhood apraxia of speech(CAS) caused by FOXP2 gene mutation, to summarize the clinical and genetic features of CAS, and to provide the basis for accurate diagnosis and outcome prediction of CAS. MethodsThe clinical features, Sanger testing, imageological examination, and follow-up of a patient carrying a heterozygous mutation of FOXP2 were summarized, and literatures about clinical features of CAS caused by FOXP2 gene mutations were reviewed. ResultsThe patient presented with language retardation at the age of 2 years and 5 months old. He was able to babble and understand parental commands but had no conscious verbal communication or spoken using phrases or "word combinations" . He was able to walk after 16 months of age. Minor morphologicals included epicanthic folds, arched eyebrows and flat-nosed. The physical examination found no abnormality while MR suggested otitis media and allergic rhinitis. The clinical-exome sequencing combined Sanger sequencing in proband confirmed a nonsense mutation in FOXP2 gene ［NM_014491: exon11, c.1432C>T(p.R478X)］, which was reported as a disease causing mutation of CAS (PMID: 27572252). The patient was diagnosed as CAS due to genetic test and clinical manifestation. The boy was followed up to 3 years old and he was able to pronounce monosyllable words and to call family member consciously. A total of 67 CAS cases that caused by FOXP2 mutations were retrieved in PubMed while there is no domestic report in CNKI and Wanfang database. All 68 cases were summarized including the case discussed in this article. The most frequent symptoms which related to speech-language disorder were abnormal pronunciation, followed by talking late, receptive and/or expressive language deficits and grammatical deficits. Moreover, multiple systems were involved with various manifestations. Thirty-four cases (50.7%) combined with neuromuscular problems. Twenty-four cases (35.8%) had craniofacial dysplasia. Twenty-one cases (31.3%) occurred below-average intelligence. Eight cases (11.9%) showed autistic features and 5 (35.8%) appeared abnormal skeletal joints. Besides, 5 cases of CAS with R478X presented with non-hearing loss, but 3 of them talked late while 1 had abnormal pronunciation and the other had difficulty in getting two words together. ConclusionGenetic test can provide the basis for accurate diagnosis of CAS and thus be helpful for appropriate treatment and family genetic counseling.
