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OBJECTIVE@#To analyze the clinical phenotype and genetic variants of a child suspected for mitochondrial F-S disease.@*METHODS@#A child with mitochondrial F-S disease who visited Department of Neurology, Hunan Provincial children's Hospital on November 5, 2020 was selected as research subject of this study. Clinical data of the child was collected. The child was subjected to whole exome sequencing (WES). Bioinformatics tools were used to analyze the pathogenic variants. Candidate variants were verified by Sanger sequencing of the child and her parents.@*RESULTS@#WES revealed that the child has harbored compound heterozygous variants of the FDXR gene, namely c.310C>T (p.R104C) and c.235C>T (p.R79C), which were inherited from her father and mother, respectively. Neither variant has been reported in HGMD, PubMed, 1000 Genomes, and dbSNP databases. Both of the variants have been suggested as deleterious according to the prediction results from different bioinformatics analysis software.@*CONCLUSION@#Mitochondrial diseases should be suspected for patients with multiple system involvement. The compound heterozygous variants of the FDXR gene probably underlay the disease in this child. Above finding has enriched the spectrum of FDXR gene mutations underlying mitochondrial F-S disease. WES can facilitate the diagnosis of mitochondrial F-S disease at the molecular level.
Subject(s)
Female , Humans , Child , Exome Sequencing , Mitochondrial Diseases/genetics , Mothers , Mutation , PhenotypeABSTRACT
Clinical data of a child with high blood ammonia and suspected argininosuccinate synthetase deficiency (ASSD) in Hunan Children′s Hospital were retrospectively analyzed, including data of mass spectra for blood amino acids and acyl carnitine, urine organic acid analysis and whole exome sequencing.After the exact diagnosis of ASSD and being approved by the Administrative Regulation for Import Medical Devices Urgently Needed in Boao Lecheng International Medical Tourism Pilot Zone of Hainan Free Trade Port, the patient was medicated with Glyceryl phenylbutyrate (GPB) and followed up.The patient was a boy aged 7 years and 8 months, who presented at the Neurology Department of Hunan Children′s Hospital for sleepiness, abnormal mental behavior and personality change for 1 week on December 2, 2021.Before GPB treatment, the highest blood ammonia, alanine aminotransferase and aspartate transaminase were 325.2 μmol/L, 465.7 IU/L and 277.3 IU/L, respectively.Genetic metabolism assay of blood and urine showed a significantly increased citrulline at 697.42 μmol/L; urine organic acid analysis showed increased urinary orotic acid at 144.2 μmol/L, and increased uracil at 65.1 μmol/L.A pure heterozygous variant of the ASS1 gene (c.1087C>T, p.R363W) was detected.After GPB treatment, the blood ammonia levels were 21.3 μmol/L, 54.6 μmol/L and 62.4 μmol/L on the 41 st, 90 th and 146 th days, respectively.Until July 20, 2022 follow-up visit, the patient recovered well without adverse events.This was the first ASSD child in China who was treated with GPB.This case report provided therapeutic experience of ASSD in our country.ASSD has a high mortality rate and unexplained abnormal mental behavior.It is necessary to timely measure blood ammonia, and a series of urea cycle disorders should be well concerned.The diagnosis and management of ASSD rely on the data of metabolism examination and genetic testing.
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Objective:To report 2 young infants of sodium channel related epilepsy with SCN2A gene mutation, and to discuss the clinical characteristics of the disease and the efficacy and safety of lacosamide combined with the literature.Methods:Corresponding information of 2 children hospitalized in the Department of Neurology of Hunan Children′s Hospital in July 2021 and October 2021 was collected, including the symptoms, comprehensive physical examination, blood, cerebrospinal fluid, imaging, electrophysiological examination, diagnosis and treatment process, response to treatment and other clinical data, as well as the sequencing results of the whole exome of the children. The efficacy and safety of lacosamide were analyzed, and the related literatures of the Biomedical Literature Database, Wanfang Data Knowledge Service Platform and Chinese Knowledge Infrastructure Database were searched and reviewed.Results:Both of the 2 cases were girl. Their onset age was within 3 months. The initial symptoms were frequent convulsions and backward development. There was no structural abnormality in the head image. The convulsions could not be controlled according to conventional multidrug treatment. The seizures were quickly controlled with lacosamide. Now they have been followed up for 6 months. No obvious adverse reactions were found. Case 1 gene test results showed the SCN2A gene (chr2:166152333-166246334) heterozygous deletion, SCN1A gene (chr2:166847754-16693013) heterozygous deletion, the deletion size being about 5.72 Mb. Case 2 gene test results showed new missense mutation of SCN2A (c.1285G>A, p.Glu429Lys). There were dozens of seizures every day. They were treated with valproic acid, oxcarbazepine and levetiracetam successively. The seizures could not be controlled. Three focal seizures originated in the left temporal region were detected by electroencephalogram. There was no recurrence on the third day after adding lacosamide, and there was no attack after 5 months of follow-up. No obvious adverse reactions were found during follow-up.Conclusions:Sodium channel related epileptic encephalopathy often starts early, has frequent seizures, and can be accompanied by backward psychomotor development at the same time. The slow sodium channel blocker lacosamide has good efficacy and safety in the treatment of sodium channel-related epilepsy with SCN2A gene mutation or combined SCN1A gene mutation.
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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.
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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.
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The changed process of bioenergy and the effects of electrode interfering on penicillin-induced epileptic brains in epileptic seizures rats were investigated. Fifty Sprague-Dawley (SD) rats were randomly divided into 4 groups, i. e. normal saline control group (group A), penicillin model group (group B), metal electrode interfere group (group C) and insulated electrode interfere group (group D). The epileptogenic potential and the expressions of the beta subunit of-ATP synthase( ATP5B) in hippocampal neurons were measured. The epileptogenic foucus potential and expressions of ATP5B in hippocampus neurons showed that the trend increased at first and decreased implantation of later, and the implantation of metal electrodes decreased the epileptogenic foucus potential at corresponding time point, but had no effect on the expressions of ATP5B. The change of epileptogenic focus potential was reduced by implantation of metal electrode, possibly due to the alteration of corrosponding bioenergy metabolism which had participated in the process of epileptic seizure.
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Animals , Male , Rats , Electrodes , Energy Metabolism , Epilepsy , Hippocampus , Mitochondrial Proton-Translocating ATPases , Genetics , Metabolism , Penicillins , Rats, Sprague-DawleyABSTRACT
Clopidogrel was believed to be superior to aspirin by the well-known CAPRIE trial. However, no other large clinical trials demonstrated the same results, but all focused on the combination use of clopidogrel with aspirin, and combination therapy in CREDO was called the "Emperor's New Clothes". However, no one overturned the results of these clinical trials by quantitatively analyzing them. We reviewed ten large-scale clinical trials about clopidogrel. On the basis of results of CAPRIE, CREDO and CHARISMA trials, we re-estimated their minimal sample sizes and their powers by three well-established statistical methodologies. From the results of CAPRIE, we inferred that the minimal sample size should be 85 086 or 84 968 but its power was only 30.70%. A huge gap existed. The same was also true of CREDO and CHARISMA trials. Moreover, in CAPRIE trial, 0 was included in the 95% confidence interval and 1 was included in the 95% confidence interval for the relative risk. There were some paradoxical data in CAPRIE trial. We are led to conclude that the results in CAPRIE, CREDO, and from the subgroup analysis in CHARISMA trials were questionable. These results failed to demonstrate that clopidogrel was superior to aspirin or that clopidogrel used in combination with aspirin was better than aspirin alone. The cost-effectiveness analyses by some previous studies were not reliable.