Research progress of dihydropyrimidinase deficiency / 中华实用儿科临床杂志

Characterized by dihydropyrimidinuria, dihydropyrimidinase (DHP) deficiency refers to a rare disorder of pyrimidine degradation, with high phenotypic heterogeneity.The disease-causing gene is DPYS, and less than 40 cases were reported worldwide.Urinary gas chromatography/mass spectrometer (GC/MS) can screen clinically suspected patients, and gene sequencing is the main means of the diagnosis of the disease.This article reviews the pathogenesis, clinical manifestation, genotype and recent research progress of the disease.

Analysis of DPYS gene variants in a child with dihydropyrimidase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with dihydropyrimidase (DHP) deficiency.@*METHODS@#High-throughput sequencing was carried out for the child. Suspected variants were verified by using Sanger sequencing.@*RESULTS@#The proband was found to carry compound heterozygous variants of the DPYS gene, namely c.1468C>T (a missense variant) and c.1339-1363del (a frameshifting variant).@*CONCLUSION@#The compound heterozygous variants of the DPYS gene probably underlie the DHP in this child. Above result has enabled genetic counseling and prenatal diagnosis for his parents.

Clinical features and ion channel gene mutations analysis in 17 cases of early-onset epileptic encephalopathy / 中华实用儿科临床杂志

Objective@#To analyze the clinical characteristics and gene mutations of early-onset epileptic encephalopathy(EOEE) caused by ion channel gene mutation, to identify the etiology, to guide the treatment and to provide the basis for genetic counseling.@*Methods@#The clinical data from 17 children with EOEE caused by ion channel gene mutation and the peripheral blood of the children and their parents were collected from June 2014 to May 2018 at the Department of Neurology, Tianjin Children′s Hospital.Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology.The mutation of pathogenic ion channel gene was found.The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified.@*Results@#Among 17 case with EOEE, 3 cases had genetic mutation, and 14 cases had denovo mutations.Dravet syndrome was found in 8 cases (47.1%), there were SCN1A gene missense mutation in 5 cases, SCN1A gene nonsense mutation in 3 cases, KCNQ2 gene missense mutation in 1 case (5.9%) and non-specific epileptic encephalopathy in 8 cases (47.1%). SCN2A gene missense mutation, SCN4A gene missense mutation, SCN8A gene missense mutation, KCNQ2 gene missense mutation and KCNH gene missense mutation were found in suspected pathogenic mutations.There were 1 missense mutation out of 5 genes, 1 missense mutation of CACNA1A gene, 1 missense mutation of GRIN2A gene and 1 missense mutation of GRIN3A gene.Seventeen patients were treated with 2 or more antiepileptic drugs, 4 with ketogenic diet and 1 with vitamin B6 supplementation.During 11 to 96 months of follow-up, seizures were completely controlled in 3 cases (17.6%), decreased in 7 cases (41.2%) by more than 50%, and decreased in 7 cases (41.2%) by less than 50%.@*Conclusions@#The clinical phenotypes for children with unexplained EOEE are varied, and gene mutations of ion cha-nnel are most common.Some gene sites are denovo mutations which have not been reported such as missense mutation for 3 case SCN1A gene, 1 case SCN2A gene, 1 case CACNA1A gene, 1 case KCNH5 gene, and nonsense mutation for 2 case SCN1A gene, which have enriched the mutation spectrum of EOEE.

Diagnosis and treatment of 64 children with viral encephalitis complicated with respiratory failure / 中国小儿急救医学

Objective To summarize the clinical features of children with viral encephalitis accompa-nied with respiratory failure,and to improve the early diagnosis and treatment. Methods The clinical data of 64 cases with viral encephalitis combined with respiratory failure in our unit from May 2005 to May 2015 were analyzed retrospectively. Results All children were characterized by sudden onset. Among them, 60 cases (93. 7%) had fever,50 cases(78. 1%) had convulsion onset,46 cases(71. 8%) had consciousness disorders, 30 cases(46. 8%) had positive pathological signs. Most of them developed respiratory failure in acute stage. Total 56 cases occurred central respiratory failure,6 cases occurred central respiratory failure with peripheral respiratory failure,2 cases occurred respiratory and circulatory failure. Total 46 cases underwent cerebrospinal fluid examination. Routine biochemical test found 32 abnormal cases,of which 10 cases had intracranial hyper-tension and 19 cases had leukocytosis,and 17 cases had increased protein content. Ten cases were positive in cerebrospinal fluid etiology examination,including herpes simplex virus positive in 8 cases,EB virus positive in 1 case,and coxsackie virus positive in 1 case. There were 6 of 64 cases with abnormal CT scans and 29 of 34 cases with abnormal MRI. The results of EEG examination were abnormal in all patients for the first time. The EEG of 48 cases showed diffuse slow waves-δ activity. EEG examination showed generalized discharges or focal discharges during treatment in 22 cases. Five cases of electrophysiological examination showed cervical spinal cord anterior horn injury. Total 24 cases were complicated with stress ulcer,4 cases with liver damage,6 cases with heart damage,4 cases with renal damage,1 case with lung damage. All cases underwent mechanical ventilation for 2-50 days. Total 33 cases(51. 5%) improved and discharged,14 cases died during hospitaliza-tion,17 cases were given up treatment. Total 25 cases had variety of neurological dysfunctions left. Total 14 cases with epilepsy were followed up for 3 months to 6 years in our department,of which 8 cases were medical-ly intractable epilepsies. Conclusion The children with viral encephalitis complicated with respiratory failure have acute onset,rapid progress,high disability and mortality. Early diagnosis and evaluation,effective mechani-cal ventilation in time,and protecting organ function,help to improve the prognosis.