Analysis of clinical phenotype and gene variation of pyridoxine-dependent epilepsy caused by ALDH7A1 gene mutation / 中华神经科杂志

Objective:To analyze the clinical phenotype and genotype characteristics of children with pyridoxine-dependent epilepsy (PDE) and provide evidence for diagnosis.Methods:Clinical data of 3 children with PDE enrolled in the Department of Neurology of Hunan Children′s Hospital from July 2016 to December 2020 were collected, and whole-exome sequencing (WES) was used for analysis. Pathogenic variants were analyzed and screened using bioinformatics tools combined with clinical phenotype. Sanger sequencing was used to analyze the source of mutations in children′s core family members.Results:Cases 1 (female) and 2 (male) were siblings, both of whom had convulsions within 24 hours after birth. WES results showed that the siblings carried compound heterozygous mutations of c.796C>T (p.R266 *) and c.1553G>C (p.R518T) in the ALDH7A1 gene, coming from the father and mother of the siblings respectively. Both of the mutations have been reported as pathogenic. Case 3, female, developed convulsions at the age of 1. WES results revealed that she carried compound heterozygous mutations of c.1094-109T>A and c.7C>T (p.R3C) in the ALDH7A1 gene, coming from her father and mother respectively. After searching HGMDPro, PubMed, 1000 Genomes, and dbSNP databases, both of the 2 mutations of c.1094-109T>A and c.7C>T (p.R3C) were not reported. The pathogenicity predictions of the 2 mutations were carried out by different biological information analysis software. The results showed that both of the mutations were harmful. All the 3 children had no epileptic seizures after treatment with increased doses of vitamin B6. Conclusions:When infants have unexplained convulsions, especially in the neonatal stage, PDE caused by ALDH7A1 gene mutation should be considered. Pyridoxine precision treatment has a good effect. The 2 de novo mutations of c.1094-109T>A and c.7C>T (p.R3C) enrich the mutation spectrum in the ALDH7A1 gene. WES has the auxiliary significance in the diagnosis of epilepsy.

Analysis of a child with carnitine palmitoyl transferase 1A deficiency due to variant of CPT1A gene / 中华医学遗传学杂志

OBJECTIVE@#To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency.@*METHODS@#Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS).@*RESULTS@#Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father.@*CONCLUSION@#CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.

Influencing factors of serum complement C3 、C4 in children with myasthenia gravis / 国际儿科学杂志

Objective Complement plays an important role in the pathogenesis of myasthenia gravis.The formation of membrane attck complex and the damage of neuromuscular junction are inseparable from the activation of complement.Then to investigate the influencing factors of serum complement C3,C4 in children with myasthenia gravis and investigate the degree of influence of related factors.Methods One hundred sixty seven cases of hospitalized or outpatient myasthenia gravis children from the Department of Neurology in Hunan Children's Hospital were collected,including 33 cases of general MG,134 cases of ocular MG,and 36 cases of normal children as control group.The concentrations of serum C3,C4,IgG,IgM,IgA,IgE were detected by immune compare turbid.The influencing factors of complement C3,C4 were investigated and compared.Results The serum C3 levels were 1.07 ± 0.22 g/L,and the serum C4 levels were(0.17 ± 0.05)g/L in the general MG.The serum C3 levels were (1.01 ± 0.20)g/L,the serum C4 levels were(0.20 ± 0.08)g/L in the ocular MG.There were(1.36 ± 0.28) g/L for C3 levels,(0.25 ± 0.11) g/L for C4 levels in the control group.Compared with the control group,there were significant difference in C3 and C4 between the general MG and ocular MG(P ＜0.01 or 0.05).The partial correlations coefficients of C3 and course of disease,IgG and C3,C3 and C4 were-0.162,0.135,0.446(P ＜0.01 or 0.05).The multiple linear regression equations were as followed:C4 =0.420 × C3,C3 =0.655 + 1.148 × C4 + 0.008 × body weight-.005 × course of disease.Using univaruate analysis,the effect factors of C4(F =18.151,P =0.000),body weight(F =6.420,P =0.003),course of disease (F =3.015,P =0.039),age × course of disease × body weight (F =2.997,P =0.042) to C3 were significant (P ＜ 0.05,or P ＜ 0.01).Conclusion The C3 levels are mainly affected by C4,body weight,duration and some interaction effects among several impact factors in children with MG.C4 is mainly affected by C3.

The clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children / 中国医师杂志

Objective To study the clinical efficacy and follow-up study of ketogenic diet adding treatment for refractor epilepsy in children.Methods Cluster sampling method was employed to select children in children's hospital from January 2015 to June 2017,a total of 25 cases were diagnosed refractor epilepsy and adding ketogenic diet.Engel grade was used to evaluate the efficiency,the side effects,electroencephalogram (EEG) changes and intellectual development at 3 months,3-6 months,and more than 6 months.Results The effective rate of epileptic seizure control was 0,66.7％ and 87.5％ at 3 months,3 -6 months and ＞ 6 months respectively.The improvement rate of EEG discharge index was 33.3％,50％ and 81.3％ respectively.The improvement of intelligence development was 33.3％,50％ and 68.8％ respectively.Gastrointestinal disturbances were the main side effects.Severe side effect occurred in two cases--they had severe food refusal and were stopped the ketogenic diet adding treament.Conclusions The ketogenic diet is effective,safe,few side effects and tolerable in infants and children with refractory epilepsy.The ketogenic diet may improve cognition and behavior in addition to reducing seizure frequency,the interical epileptiform discharges (IED) index and improve the quality of life of epileptic children.However,the acceptance of ketogenic diet therapy for children is not satisfactory.The sample size is small and needs further promotion.While large samples and long-term observations are still desired to better recipes,and to provide possibly effective altemative to other therapies for refractor epilepsy.

The analysis of failure cause of valproate monotherapy for newly diagnosed generalizedepilepsy in children / 中国神经精神疾病杂志

Objectives To investigate the failure cause of valproate monotherapy for newly diagnosed generalized epilepsy in children and to investigate the factors related to the failure. Methods The newly diagnosed cases of general?ized epilepsy were recruited and given valproate monotherpy. After 2 years of treatment and regular follow-up, they were divided into control group and poor effect group.according to their response to the treatment. The clinic data and electro?encephalogram were collected. The reasons of treatment failure were studied using Logistic regression analysis. Results There were 231 patients who had completed this study in all. After 2 years, 62 cases had switched to other drugs because of poor efficacy. Efficacy of was satisfactory in 169 cases of children. There were 3 cases of poor compliance, and one case switched to other drug due to side effect. There were statistically significant (P<0.05) in the abnormal electroenceph?alogram (EEG) rate (poor effects group 90.32%vs. control group 61.54%), abnormal cranial magnetic resonance imaging (MRI) rate (poor effects group 45.16%vs. control grou p23.08%) and the first age of onset [poor effects group 0.50(0.42, 2.50)year vs. control group 0.75(1.50, 5.16)year] between the good effects group and poor effects group. Univariate anal?ysis showed that mental retardation,birth asphyxia,abnormal bain MRI,the first episode of age were statistically signifi? cant different between these two groups (P<0.05). Further multivariate regression analysis showed that the low first onset age (OR=2.124 P=0.004)、mentalretardation (OR=10.535,P=0.000, abnormal brain MRI(OR=1.603,P=0.020), asphyxia at birth(OR=1.913 P=0.027)were independent risk factors for the poor efficacy of valproate. Conclusions The main rea?sons for the failure of valproate monotherpy in children with generalizedepilepsy are poor efficacy,bad compliance, ad?verse reactions. The risk factors of poor efficacy are the low first onset age, mental retardation, abnormal brain MRI and asphyxia at birth etc.

Clinical features of the variants of benign childhood epilepsy with central temporal spikes: 12 cases report / 临床儿科杂志

Objective To study the clinical features of the variants of benign childhood epilepsy with central temporal spikes (BECT).Methods The clinical data of 12 hospitalized pediatric patients with BECT from Jan 2007 to Jan 2014 were retrospectively reviewed. Results There were 7 boys and 5 girls in 12 patients. The age of onset was from 3 to 9 years old. Two cases were dizygotic twins. The atypical symptoms included atypical absence of 10 cases, negative myoclonic seizure of 8 cases, speech expression disorders and oral-pharynx apraxia of 4 cases. The electroencephalography (EEG) of all 12 patients showed abundance of spike and waves (SW) in rolandic areas during wake-up and sleep. The SW index was 50%-85% during slow sleep in all patients.Conclusions The variants of BECT are often associated with EEG deterioration. Understanding the clinical featuress and EEG characteristics can help the diagnosis of BECT variants.

An analysis of clinical etiologies about stroke in 157 children / 临床儿科杂志

Objective To analyze the potential etiologies and risk factors of childhood stroke. Methods This study retrospectively reviewed the clinical data of 159 children who were admitted from Jan.2006 to Jan.2014. Results The 159 children were composed of 100 boys and 59 girls , with median onset age of 1.8 years (ranged from 1 day to 12 years old) and median peak age of 0.9 years (ranged from 3 months to 2.8 years old). Their initial symptoms included limb hemiplegia,language dififculties and convulsion. The common causes included infections found in 46 cases (central nervous system infection in 32 cases, respiratory and gastrointestinal tract infection in 14 case), head injury in 42 cases, vitamin K deifciency in 29 cases, Moyamoya disease in 8 cases, heart diseases in 11 cases, spontaneous hemorrhage in 11 cases and 12 cases of unknown reason. Infectious diseases were the most common cause of children acute ischemic stroke in toddler period;and vitamin K1 deifciency were the most common cause of children hemorrhage stroke in infancy. The most common region of infarction is basal ganglia and middle cerebral artery in neuronal imaging. The median age at the time of diagnosis was 1.4 days. The median time of inhospital was 28 days. The median apex time was 4.3 days. Conclusions Among 159 cases, acute ischemic stroke is much more common than hemorrhagic stroke in children stroke, and the major risk factors are infections and head injury;Vitamin K1 deifciency is a major risk factor in infants with hemorrhagic stroke.

Clinical analysis of 62 cases of convulsion associated with acute purulent meningitis of children / 中国医师杂志

Objective The study was conducted to investigate the acute phase of convulsion related problem on the clinical manifestations,imaging and electroencephalograph (EEG) examination of purulent meningitis.Methods Cluster sampling method was employed to select children in our hospital,a total of 301 cases with purulent meningitis was analyzed retrospectively.Among them,62 cases had convulsion.The incidence of convulsion in the acute phase of the purulent meningitis,risk factors,and prognosis were analyzed.Results The convulsion incidence rate of acute purulent meningitis was 20.60％.The partial seizure was eight cases (12.90％).The secondarily generalized seizure following partial seizure was 15 cases (24.19％).The generalized seizure was 32 cases (51.61％).The convulsive status was 7 cases (11.29％).The EEG abnormality was significantly different between the convulsion group and the no convulsion group (P ＜ 0.05).The incidence of brain organic damage was significantly different between two groups (P ＜0.05).The multivariate unconditional logistic regression analysis showed,cause of disease,first symptom,disturbance of consciousness,obvious signs,and cerebrospinal fluid culture with convulsion were the relevant factors (P ＜ 0.01).Conclusions The most common seizure of purulent meningitis was the generalized seizure.Brain organic damage easily resulted in convulsion of purulent meningitis.The days of hospitalization,cause of disease,first symptom,disturbance of consciousness,obvious signs,and cerebrospinal fluid culture with convulsion were the positively relevant factors.Those positively relevant factors in combination of the clinical manifestations,imaging,and EEG examination in children would play an important role in diagnosis,treatment,and prognosis evaluation of convulsion derived from purulent meningitis.Moreover,convulsion affects the disease recovery in children with purulent meningitis.

Clinical characteristics, etiology and long-term outcome of childhood epilepsia partialis continua / 临床儿科杂志

Objectives To investigate etiology, clinical characteristics and outcome in children with epilepsia partialis continua (EPC). Methods Sixty-three pediatric patients with EPC were retrospectively analysed. The patients aged (5.53±3.65) years old, with brain CT scans or MRIs after diagnosis, basic laboratory tests, cerebrospinal lfuid analysis and electroencephalog-raphy. The average follow-up time was (22.19±21.19) months (6-72 months). Results The median duration of EPC was 11 days (1-180 days). The causes of EPC were inlfammatory and immune-mediation (36 cases, 57.14%, Rasmussen’s encephalitis included), metabolic disorders (8 cases, 12.70%), brain structure abnormalities (5 cases, 7.94%), vascular malformation (5 cases, 7.94%), dual causes (3 cases, 4.76%), post brain surgery (2 cases, 3.17%) and cryptogenic pathogenesis (4 cases, 6.35%). Neurological dysfunc-tions were observed in 44 cases (69.84%). Age, routine cerebrospinal lfuid abnormalities, the presence of inlfammation and im-mune mediated, EPC long duration, involving the right upper extremity were the risk factors of poor prognosis. Conclusions The most common causes of childhood EPC are inlfammation and immune-mediated central nervous system diseases. Patients with early age of onset, a great tendency of longer duration of EPC and cerebrospinal lfuid abnormalities, involving the right upper ex-tremity have a poor prognosis.