成人发病甲基丙二酸血症的临床分析

甲基丙二酸血症(methylmalonic acidemia,MMA)是一种有机酸血症,属于常染色体隐性遗传病,主要是由于甲基丙二酰辅酶A变位酶(methylmalonyl-COA mutase,MCM)缺陷及其辅酶硫胺素代谢障碍导致机体三羧酸循环及氧化磷酸化障碍.     

迟发型甲基丙二酸血症6例报道并文献复习

正甲基丙二酸血症(methylmalonic acidemia,MMA)或称甲基丙二酸尿症(methylmalonic aciduria,MMA)是先天性有机酸代谢异常中最常见的疾病,为常染色体隐性遗传。临床上有单纯性甲基丙二酸血症(MMA)和甲基丙二酸血症合并同型半胱氨酸尿症(MMA-HC)两种类型。由于甲基丙二酰辅酶A变位酶或其辅酶钴胺素(维生素B12)代谢缺陷导     

以精神症状初发的甲基丙二酸尿症伴同型半胱氨酸血症1例

甲基丙二酸尿症是遗传性有机酸代谢异常中最常见的病种,主要因甲基丙二酰辅酶A变位酶(MCM)缺陷及其辅酶钴胺素(维生素B12)代谢缺陷引起。以精神症状初发的甲基丙二酸血症,鉴别诊断困难。本文旨在详细阐述该案例的诊治过程,并进行文献复习。     

少年起病的甲基丙二酸血症1例报告并文献复习

甲基丙二酸血症(MMAemia)为1组常染色体隐性遗传的代谢性疾病,是由于线粒体内的甲基丙二酰辅酶A变位酶(MCM)或其辅酶脱氧腺苷钴胺素(AdoCbl)先天性缺陷,使体内物质代谢的中间产物甲基丙二酸(MMA)不能进一步分解,在体内堆积引起的以神经系统损害和酸中毒为主的临床综合征。据估计全球发病率约为五万分之一,我国尚无相关统计。目前国内报告的病例多是婴幼儿起病,少年期起病的少见,现将我们发现的1例少年期起病的MMAemia,报告如下。1资料1．1发病经过:患者男,10岁。因行走不稳2个月,于2005年8     

晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症1例报告并文献复习

目的 探讨晚发型甲基丙二酸尿症合并同型半胱氨酸血症的临床及基因变异特点。方法 回顾性分析1例MMACHC基因突变致晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症患者的临床资料及基因检测结果，并结合文献讨论。结果 本例男性患者，以双足麻木起病，逐渐出现双下肢僵硬无力，发病前有非特异性精神行为异常症状，此次就诊经基因检测发现MMACHC基因4号外显子存在c. 482G>A(p. Arg161Gln)错义突变，与文献报道c. 482G>A复合杂合突变不同，本例患者突变类型为纯合突变。结论 甲基丙二酸尿症合并同型半胱氨酸血症的临床异质性较大，容易漏诊误诊，当出现不明原因的精神行为异常时应考虑该诊断，基因检测是诊断的重要依据，同时也可指导该病的分型。     

维生素B_(12)依赖型甲基丙二酸血症一家系临床表型和基因突变分析及疗效评价

目的探讨维生素B_(12)依赖型甲基丙二酸血症家系临床特点、基因突变和维生素B_(12)治疗效果。方法采集一维生素B_(12)依赖型甲基丙二酸血症家系共4名成员临床资料,抽取外周静脉血行血浆氨基酸和酰基肉碱谱分析及基因检测,评价维生素B_(12)治疗效果。结果家系中先证者12岁发病,以学习成绩下降、性格改变为首发症状,病程中出现幻觉、双下肢无力;先证者之弟主要表现为易怒、学习成绩较差。经血浆氨基酸和酰基肉碱谱分析,先证者及其弟血浆丙酰肉碱、丙酰肉碱/乙酰肉碱比值升高,尿液甲基丙二酸水平升高。基因检测显示,先证者及其弟均存在MMACHC基因复合杂合突变c.482GA(p.Arg161Gln)和c.609GA(p.Trp203X),其父携带MMACHC基因错义突变c.482GA(p.Arg161Gln),其母携带MMACHC基因无义突变c.609GA(p.Trp203X)。经维生素B_(12)治疗后均症状好转。结论晚发型维生素B_(12)依赖型甲基丙二酸血症系MMACHC基因复合杂合突变所致,维生素B_(12)治疗反应良好,早期诊断、及时治疗对患者预后意义重大。     

脑脊髓炎样起病的成人型甲基丙二酸血症1例临床分析及文献复习

正甲基丙二酸血症(methylmalonicacidemia,MMA)是最常见的有机酸代谢病之一,由于甲基丙二酰辅酶A变位酶(MCM)或其辅酶钴胺素(Cb)的缺陷所致,属于常染色体隐性遗传疾病。它引起神经、肝脏、肾脏等多系统损害外,还可能导致静脉血栓形成、病理骨折、血氨升高,目前病理骨折及血氨升高在国内尚无报道。多系统症状同时出现在该例患者,临床实属罕见。1临床资料     

短链脂酰辅酶A脱氢酶缺陷综合征一家系临床表型及基因突变分析

目的总结短链脂酰辅酶A脱氢酶缺陷综合征临床表型和基因突变特点。方法与结果女婴患儿,1个月14 d,临床表现为智力和运动发育迟滞、肌张力下降、癫发作,发作类型为痉挛发作和全面性强直发作;体格检查可见左侧面部和左上腹部咖啡牛奶斑;尿液乙基丙二酸、甲基琥珀酸和全血丁酰肉碱水平升高;发作间期视频脑电图可见爆发-抑制波形;头部MRI显示,左侧大脑半球和右侧额叶皮质发育畸形;基因检测显示,患儿存在ACADS基因c.795+1GA纯合突变,分别来自携带该位点杂合突变的父母。患儿明确诊断为短链脂酰辅酶A脱氢酶缺陷综合征,该家系明确诊断为短链脂酰辅酶A脱氢酶缺陷综合征家系。在服用泼尼松4 mg/(kg·d)和左乙拉西坦30 mg/(kg·d)基础上,增加维生素B210 mg/(kg·d)口服。随访至今,未再出现癫发作。结论短链脂酰辅酶A脱氢酶缺陷综合征临床表现为智力和运动发育迟滞、肌张力下降和早发性癫性脑病,尿液乙基丙二酸、甲基琥珀酸和全血丁酰肉碱升高,并可能导致皮质发育畸形。ACADS基因c.795+1GA纯合突变可以致病,为首次报道。     

以小脑损害为主要表现的成人甲基丙二酸血症合并高同型半胱氨酸血症一例

报告1例成年起病的甲基丙二酸血症合并高同型半胱氨酸血症患者的临床资料。患者为男性,24岁发病,以行走不稳、精神行为异常起病,进行性加重,神经系统体检发现明显的小脑性共济失调及锥体束征,头颅磁共振成像显示双侧小脑半球对称性长T2信号,血液总同型半胱氨酸、尿甲基丙二酸水平显著增高,基因检测发现MMACHC基因复合杂合突变c.482G>A及c.217C>T,确诊为钴胺素C缺乏症。经给予腺苷钴胺、甜菜碱、叶酸、左卡尼汀治疗后患者行走不稳略有所好转,血同型半胱氨酸水平也显著下降。     

短链烯酰辅酶A水合酶1基因突变导致线粒体短链烯酰辅酶A水合酶1缺乏症1例

目的总结1例短链烯酰辅酶A水合酶1(ECHS1)基因导致线粒体短链烯酰辅酶A水合酶1缺乏症(ECHS1D)患儿的临床特征及基因突变特点。方法回顾性分析2021年1月就诊于徐州市儿童医院神经内科的1例ECHS1D患儿的临床特点及基因检测结果, 并通过检索国内外相关文献对该疾病的临床特征进行复习。结果患儿男性, 年龄6个月4 d, 急性起病, 临床以肢体活动障碍为主要表现。患儿运动发育迟缓, 竖头尚可, 不能翻身、独坐, 不能追视, 不能逗笑出声, 四肢肌张力增高。入院检查示血乳酸水平升高至6.2 mmol/L, 提示代谢性酸中毒。头颅磁共振成像(MRI)示双侧基底节区异常信号, 左侧大脑半球脑膜异常强化。全外显子组测序发现该患儿ECHS1基因存在复合杂合突变, 分别为c.563C>T(p.A188V)和c.5C>T(p.A2V), 患儿父亲携带c.563C>T突变, 母亲携带c.5C>T突变, 均为错义突变。结论 ECHS1基因以错义突变为主, 大部分为复合杂合突变, 少部分为纯合突变。ECHS1基因突变导致线粒体ECHS1D常累及婴幼儿, 发病相对较早, 临床表...     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.