Objective:To investigate the efficacy and safety of ketogenic diet (KD) therapy in the epilepsy of infancy with migrating focal seizures (EIMFS) associated with TBC1D24 gene mutation.Methods:Clinical data of two children with TBC1D24 gene-related EIMFS were collected retrospectively, who were admitted to Department of Pediatrics, Fujian Medical University Union Hospital from 2019 to 2020. Their clinical characteristics and the efficacy and safety of KD therapy were analyzed, and literature review was conducted.Results:Seizures were onset before six months old in the two children with TBC1D24 gene-related EIMFS. Multifocal myoclonic seizures were manifested and happened frequently, lasting for more than 30 minutes sometimes. Developmental retardation was obvious in the two children. A small amount of focal sharp, spike, sharp-slow complex, and spike-slow complex waves were showed in the interictal electroencephalography (EEG). TBC1D24 gene mutations were found in the two children, one with a compound heterozygous mutation (c.1025C>T, p.S342L; c.229_c.240delATCGTGGGCAAG,p.I77_K80del), and the other with a homozygous mutation [c.119G>A,p.R40H(Arg40His)]. Both of those were potentially pathogenic. A variety of anti-epileptic drugs showed poor outcome for the two children. The epilepsy was drug-refractory one. After four to 17 months of KD therapy, the epilepsy in the two children was controlled effectively. There was not obvious adverse reactions. Among six children with TBC1D24 gene-related EIMFS in the literature review, four cases were effective or partially effective for KD therapy, one was discontinued due to insufficient ketogenic ratio, and one was discontinued without effect. There were no obvious adverse reactions in the six children.Conclusions:TBC1D24 gene-related EIMFS is mostly drug-refractory epilepsy. Early KD therapy may help to control seizures.

60 years, 13.3% of the total sarcoidosis patients) diagnosed as sarcoidosis based on national criteria from the year 1965 through 1999 were reviewed. Results The clinical degree was as follows: phase I, 8 cases; phase Ⅱ, 6 cases; phase Ⅲ, 2 cases. The elderly sarcoidosis patients manifested variously, with misdiagnosis rate being 50%. The active degree of pulmonary sarcoidosis was correctly evaluated after the diagnosis was confirmed and the patients was strictly observed during the treatment since it was very important for avoiding the occurrence of complications. Conclusions The early diagnosis in elderly patients with sarcoidosis should be emphasized to prevent them from missing and misdiagnosis. The elderly patients with treating indications in phases Ⅱ and Ⅲ could be given steroids and constant observation and regular examinations are important during the treatment.

Objective:To explore the relationship between serum cortisol and attention deficit hyperactivity disorder (ADHD), and to investigate the application of cortisol in the diagnosis of ADHD, so as to provide clues and theoretical basis for the comprehensive prevention and treatment of ADHD in the future.Methods:Serum cortisol levels were detected in 159 ADHD children [ADHD group, 58 cases of predominately inattentive presentation (ADHD-I), 32 cases of predominately hyperactive/impulsive presentation (ADHD-HI), 69 cases of combined presentation (ADHD-C)], and 58 healthy control children (healthy control group) from July 2018 to June 2019, at Fujian Medical University Union Hospital.The receiver operating characteristic (ROC) was used to evaluate the diagnostic value of serum cortisol levels in ADHD groups.Results:(1) The serum cortisol levels of ADHD-I group[(216.58±70.55) nmol/L], ADHD-HI group[(182.26±51.34) nmol/L]and ADHD-C group[(222.81±75.70) nmol/L]were significantly lower than that of the healthy control group[(344.83±98.17) nmol/L](all P<0.001). The level of cortisol in ADHD-HI group was lower than that in ADHD-I group and ADHD-C group ( P<0.05). (2)According to the ROC analysis of serum cortisol, the area under the ROC curve for the diagnosis of ADHD group was 0.866 (95% CI: 0.814-0.917), the maximum Youden index was 0.583, the corresponding sensitivity was 89.3%, the specificity was 69.0%, and the cut-off was 302.88 nmol/L.When the specificity was 85.0%, 246.13 nmol/L was the diagnostic threshold and its corresponding sensitivity was 71.1%.Under the ROC curve for the diagnosis of ADHD-I group, the area was 0.857 (95% CI: 0.792-0.922), the maximum Youden index was 0.552, the corresponding sensitivity was 69.0%, the specificity was 86.2%, and the cut-off was 243.39 nmol/L.Under the ROC curve for the diagnosis of ADHD-HI group, the area was 0.934 (95% CI: 0.887-0.980), the maximum Youden index was 0.745, the corresponding sensitivity was 96.9%, the specificity was 77.6%, and the cut-off was 261.55 nmol/L.Under the ROC curve for the diagnosis of ADHD-C group, the area was 0.841 (95% CI: 0.774-0.908), the maximum Youden index was 0.559, the corresponding sensitivity was 87.0%, the specificity was 69.0%, and the cut-off was 302.82 nmol/L.In view of parents′ lack of understanding of ADHD behavior, it is suggested that the diagnostic threshold of cortisol level of 246.13 nmol/L should be based on 85.0% specificity principle, combined with behavior verification in clinical practice, so as to improve the diagnostic accuracy. Conclusions:Cortisol levels in ADHD-I, ADHD-HI and ADHD-C groups are lower than that in control group.There is functional impairment of hypothalamic-pituitary-adrenal axis in ADHD children.The level of cortisol has certain accuracy in the diagnosis of simple ADHD and can be used in clinical diagnosis.

OBJECTIVETo review the clinical features of a families affected with glutaric acidemia type I (GA-1) and screen potential mutations in glutaryl-CoA dehydrogenase (GCDH) gene.

METHODSClinical data of the patients and their family members was analyzed. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.

RESULTSTwo patients have manifested macrocephaly. Imaging analysis revealed arachnoid cyst and subdural effusion. The elder sister had encephalopathy crisis. The younger sister had significantly raised glutaric acid, whilst the elder sister was normal during the non-acute phase. Genetic analysis has revealed a homozygous c.1244-2A> C mutation of the GCDH gene in both patients.

CONCLUSIONThe clinical features and mutation of the GCDH gene have been delineated in a Chinese family affected with GA-1. The c.1244-2A> C mutation may be particularly common in the Chinese population.

Adolescent ; Amino Acid Metabolism, Inborn Errors ; diagnostic imaging ; enzymology ; genetics ; Base Sequence ; Brain Diseases, Metabolic ; diagnostic imaging ; enzymology ; genetics ; China ; DNA Mutational Analysis ; Family Health ; Female ; Genetic Predisposition to Disease ; genetics ; Glutaryl-CoA Dehydrogenase ; deficiency ; genetics ; Homozygote ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Mutation ; Radiography

Objective:To observe the clinical effect of Perampanel on the add-on therapy in children with drug-resistant epilepsy.Methods:Clinical data of children with drug-resistant epilepsy treated with add-on therapy of Perampanel in the Department of Pediatrics, Fujian Medical University Union Hospital from January to June 2020 were retrospectively analyzed, aiming to assess the therapeutic efficacy of Perampanel on the add-on therapy of drug-resistant epilepsy.The self-control effective rate of Perampanel before and after treatment were counted.Results:A total of 20 cases of 2-12 year-old children with drug-resistant epilepsy were collected, including 14 males and 6 females.Their mean age, age of onset and course of disease were (5.82±2.39) years, (3.41±1.96) years and (2.40±1.48) years, respectively.Among them, 1 case had simple partial seizures, 7 cases had complex partial seizures, 1 case had generalized seizures and 5 cases had epilepsy syndromes, there were 6 cases with undetermined seizure attack.After 3-month add-on therapy of Perampanel, 4 cases of children with drug-resistant epilepsy were seizure-free, 8 cases had the reduced frequency of seizure for 50% or more, 2 cases had the reduced duration of seizure, 1 case had the reduced severity of seizure, while 4 cases did not respond to perampanel and 1 case was aggravated.Based on the criteria of reduced frequency of seizure for more than 50%, the therapeutic efficacy of add-on therapy of Perampanel achieved 60% in children with drug-resistant epilepsy.Conclusions:The third generation of anti-seizure medication Perampanel can effectively reduce the frequency of seizure, especially in the elder children and those with certain epilepsy syndromes.

The clinical data of a child with MORC2 gene mutation related neurodevelopmental disorder treated in Fujian Medical University Union Hospital in July 2020 were analyzed retrospectively.The male (7-year-old)patient was global retardation from infant, with special face, short stature, small head circumference, decreased muscle strength and positive pyramidal tract sign of lower limbs.Brain magnetic resonance imaging was similar to the changes of Leigh syndrome.Genetic testing found de novo mutation in MORC2 gene chr22: 31345763, c.292G>A(p.Gly98Arg). And literature review found that there was only one related report. MORC2 gene mutation related neurodevelopmental disorder is a newly discovered syndrome, and c. 79G>A(p.Glu27Lys) is the most common mutation.This case enriched the clinical phenotype and genotype of neurodevelopmental disorder related to MORC2 gene.

Objective: To explore the efficacy and safety of clonidine adhesive patch in Tourette syndrome (TS) patients with comorbid attentiondeficit/hyperactivity disorder (ADHD). Methods: This study was conducted on a sample of children and adolescents with TS who had comorbid ADHD between May 2012 and March 2015. The patients were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, and were randomly assigned to four different dose groups: 1.0 mg/week, 1.5 mg/week, 2.0 mg/week and placebo group, and the symptom was evaluated by Swanson, Nolan, and Pelham Rating Scale, Version IV (SNAP-IV) and Yale Global Tic Severity Scale scales every 2 weeks. The primary outcome was tic disorders (TD) effective rate at week 8. Results: One hundred and twenty-seven TS patients with comorbid ADHD in 2.0 mg/week (n=35), 1.5 mg/week (n=27), 1.0 mg/week (n=36) and placebo groups (n=29) were included in this subgroup analysis. The TD effective rate of the 2.0 mg, 1.5 mg, and 1.0 mg groups at week 8 were significantly better than that in placebo group (85.7%, 81.5%, and 86.1% vs. 20.7%, all p<0.0001). All groups demonstrated significant improvements in SNAP-IV total scale scores compared to baseline (p=0.0004), with treatment groups showing only a trend for better performance compared to placebo group at week 8, without statistical differences (22.1±15.41, 21.3±11.96, and 21.2±12.48 vs. 26.0±13.37, p=0.3385). A total of 9 adverse reactions occurred, all recovered spontaneously without additional medication. Conclusion Clonidine adhesive patch could safely and effectively reduce the tic symptoms of TS patients with comorbid ADHD, and might be potentially helpful in the ADHD symptoms control.

Tic disorder (TD) is a neurodevelopmental disorder that occurs in childhood, characterized by involuntary movements or vocal tics and occasionally accompanied by various comorbidities.It may seriously affect children′s daily life, learning and social activities.Exploring its etiology and pathological mechanisms and developing drugs require extensive research on animal models.There are currently various methods for constructing TD models, including induced and spontaneous animal models, such as induced animal models with abnormal neurotransmitters and immune functions and spontaneous animal models based on genetic engineering.However, no animal model can fully match the manifestations of TD.This article summarizes the commonly used animal models for TD to provide references for exploring pathological mechanisms and developing drugs.

Objective: To delineate the clinical and genetic features of two pedigrees affected with aromatic L-amino acid decarboxylase (AADC) deficiency. Methods: The clinical features, family history and results of genetic testing of 2 patients with AADC deficiency were retrospectively analyzed. Results: Both patients featured hypotension, developmental delay and oculogyric crisis during infancy.Genetic testing confirmed that they have respectively carried c. 714+ 4 (IVS6) A>T/c.175(exon2)G>A compound heterozygous variants and c. 714+ 4(IVS6)A>T homozygous variant. Conclusion The clinical manifestation of children with AADC deficiency may include hypotonia, developmental delay and paroxysmal oculogyric crisis. The combination of 3-O-methyldopa testing and variant analysis is not only very useful for early diagnosis, but also important for the evaluation of treatment effect and prognosis of the disease. Discovery of the novel variants has enriched the variant spectrum of AADC deficiency.