婴幼儿遗传代谢性疾病的临床、影像学特点及串联质谱筛查

先天性代谢缺陷病（IEM）或称遗传代谢性疾病（IMD）是由于基因突变导致机体生化物质在合成、代谢、转运和储存等方面出现异常的总称。IMD可发生于各个年龄阶段,以新生儿和婴幼儿期多见^[1],常造成脑部损伤。随着生化及影像学的发展,对IMD的认识进一步加深,现将其临床、影像学特点及串联质谱（MS/MS）筛查情况综述如下。1临床特点虽然IMD临床表现不典型,但是新生儿期发病者多有如下特点：①病情重,进展快,病死率高。     

围生期脑损伤与儿童癫痫性脑病关系分析

目的回顾性分析儿童癫痫性脑病的临床特点。方法依据国际抗癫痫联盟，对70例儿童癫痫性脑病患者围生期损伤因素、智力行为倒退的临床表现、影像学资料、病因学分析、治疗的反应进行总结。结果癫痫分类中以婴儿痉挛最多52例（74．3％）。病因中，围生期因素46例（65．71％），遗传代谢病21例（30．00％），智力运动倒退者64例（91．4％）。59例进行头颅CT检查，9例正常，50例异常者中有脑发育不良5例，胼胝体缺如2例，结节性硬化5例，硬膜下积液7例，颅内出血8例，缺氧缺血性脑病23例。平均随访期限为23个月，40例患者用ACTH治疗，21例治疗有反应，2例痊愈。对所有病例进行0～6岁Gesell发育筛查测试（DST），治疗后DST值高于治疗前（P〈0．01）。结论围生期脑损伤仍然是癫痫性脑病的第一病因。     

儿童阻塞性睡眠呼吸暂停低通气综合征与代谢性疾病

随着儿童肥胖发病率的增加,儿童阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的发病率也明显增加.肥胖已成为继腺样体和(或)扁桃体肥大后儿童OSAHS发病的第二大危险因素.儿童OSAHS和肥胖可能共同导致了代谢性疾病.OSAHS导致代谢异常可能与氧化应激、炎性反应和脂肪因子的释放有关.手术治疗是儿童OSAHS的首选治疗方法,而且能有效改善代谢异常,减少炎性反应因子的释放,改善血脂紊乱、呼吸暂停低通气指数和睡眠结构异常.     

儿童遗传代谢性肝病诊治现状及展望

代谢性肝病是儿童肝损伤的病因之一,因其复杂的临床表现及常规诊断方法的局限,难以早期诊断。检测技术水平的进步为儿童代谢性肝病早期确诊奠定了基础。如能早期确诊,通过适当的饮食或药物治疗,一部分代谢性肝病预后良好。今后应注重儿童代谢性肝病的预防,加强基础与临床的进一步研究,为诊断及治疗提供新的手段和方法。     

琥珀酸与代谢性疾病的研究进展

琥珀酸是细胞线粒体三羧酸循环的中心代谢产物,同时也是肠道菌群重要的代谢产物。大量证据表明琥珀酸以“信号分子”的方式参与代谢性疾病的发生、发展以及转归。肥胖、非酒精性肝炎、2型糖尿病、代谢性心血管疾病与代谢稳态失衡密切相关,本文综述了琥珀酸与这4种代谢性疾病之间的关系及其作用机制,以期为代谢性疾病的预防和治疗提供新的思路和策略。     

肠道菌群与代谢性疾病

肠道微生物数量庞大、种类繁多,在机体中参与了各种代谢活动,发挥着重要的作用。近年来,随着人们生活水平的提高,饮食结构偏重于高脂肪、高蛋白,导致了肥胖以及三高等代谢性疾病,引起了科研工作者得广泛关注。大部分研究结果显示,肠道菌群与代谢性疾病存在着一定的联系,本文针对此问题作一综述。     

Irisin与代谢性疾病的关系

Irisin是新发现的一个多肽激素,可对脂肪的分解代谢和体温调节产生作用.作为一个代谢性调控激素,irisin可能参与代谢性疾病的发生、发展.研究显示,肥胖引起irisin分泌增加,血浆irisin与体重、体重指数、腰围、体脂量呈正相关;2型糖尿病患者血浆irisin水平明显降低,原因可能与irisin分泌代偿能力渐失、药物治疗、肾功能受损、胰岛素敏感性下降等因素有关;非酒精性脂肪性肝病患者血浆irisin水平明显升高;代谢综合征患者血浆irisin水平与甘油三酯和低密度脂蛋白-胆固醇呈正相关.     

乳清蛋白对代谢性疾病作用的研究进展

<正>乳清蛋白饮食被认为是预防和治疗人类和动物肥胖和糖尿病的方法之一。乳清蛋白可以降低健康人群的血糖,降低糖尿病和肥胖患者的葡萄糖耐量;减轻体重;维持肌肉质量;增加人体释放厌食激素如胆囊收缩素、瘦素和胰高血糖素样肽(GLP)-1;减少食欲激素和生长素释放肽的释放。乳清蛋白还可以降低血压和血脂。口服补充乳清蛋白有助于控制多种代谢性疾病,本文综述乳清蛋白对代谢性疾病的作用研究进展。1 乳清蛋白的主要营养和功能成分乳清蛋白是乳清中的一种可溶     

累及心脏的线粒体代谢性疾病的诊断

代谢性疾病由于产生能量代谢异常或致代谢中间产物蓄积，因而常引起心脏病变。2003年第1届世界小儿与青少年心衰学术会议上，Lipshultz报告病因明确的儿童扩张性心肌病患儿384例，其中先天性代谢疾病致心肌病30例，可见代谢性疾病引起的心肌病变不少见。现就线粒体代谢异常致心脏病的特点综述如下。     

Transplantation in inborn errors of metabolism: current considerations and future perspectives

Inborn errors of metabolism (IEM) comprise an assorted group of inherited diseases, some of which are due to disordered lysosomal or peroxisomal function and some of which might be improved following haemopoietic cell transplantation (HCT). In these disorders, the onset in infancy or early childhood is typically accompanied by rapid deterioration, resulting in early death in the more severe phenotypes. Timely diagnosis and immediate referral to an IEM specialist are essential steps in optimal management. Treatment recommendations are based on the diagnosis, its phenotype, rate of progression, prior extent of disease, family values and expectations and the risks and benefits associated with available therapies, including HCT. International collaborative efforts are of utmost importance in determining outcomes of therapy for these rare diseases, and have improved those outcomes significantly over recent decades. This discussion focusses on HCT in IEM, providing an international perspective on progress, limitations, and future directions.     

Epilepsy and inborn errors of metabolism in children

Epilepsy is a frequent symptom in inborn errors of metabolism, with virtually no specific seizure types or EEG signatures. It is most important to look quickly for those few inborn errors of metabolism in which specific therapies such as supplementation of cofactors or diets can make all the difference. If these investigations remain negative, epilepsy has to be treated with conventional antiepileptic drugs. Still, epilepsy is a potentially treatable symptom of many inborn errors of metabolism, and optimal treatment is of great importance for patients and their families.     

Epilepsy and inborn errors of metabolism in adults: A diagnostic approach

Summary Inborn errors of metabolism (IEMs) represent poorly known causes of epilepsy in adulthood. Although rare, these are important to recognize for several reasons: some IEMs respond to specific treatments, some antiepileptic drugs interfering with metabolic pathways may worsen the clinical condition, and specific genetic counselling can be provided. We review IEMs potentially revealed by epilepsy that can be encountered in an adult neurology department. We distinguished progressive myoclonic epilepsies (observed in some lysosomal storage diseases, respiratory chain disorders and Lafora disease), from other forms of epilepsies (observed in disorders of intermediary metabolism, including porphyrias, creatine metabolism defects, glucose transporter (GLUT-1) deficiency, Wilson disease or succinic semialdehyde dehydrogenase deficiency). We propose a diagnostic approach and point out clinical, radiological and electrophysiological features that suggest an IEM in an epileptic patient. Competing interests: None declared     

Thiamine-responsive inborn errors of metabolism

Three different inherited disorders are known in which thiamine may exert a beneficial effect: maple syrup urine disease (MSUD), lactic acidaemia and the syndrome of megaloblastic anaemia with sensorineural deafness and diabetes mellitus. The amounts of thiamine which were used for long-term treatment varied from 20 to 2400 mg day^?1. Additional treatment, such as the reduction of dietary branched chain amino acids in MSUD, could not be omitted in some cases. It has been shown that the vitamin improves the stability of the branched chain ketoacid decarboxylase, although some weeks may be needed to observe thein vivo effect of treatment. A prolonged trial with high doses of thiamine should always be given.     

Parkinsonism and inborn errors of metabolism

Parkinsonism is a frequent neurological syndrome in adulthood but is very rare in childhood. Early forms of Parkinsonism have many distinctive features as compared to Parkinsonism in adults. In fact, rather than Parkinsonism, the general concept “hypokinetic-rigid syndrome” (HRS) is more accurate in children. In general, the terms “dystonia-parkinsonism”, “parkinsonism-plus”, or “parkinsonism-like” are preferred to designate these forms of paediatric HRS. Inborn errors of metabolism (IEM) constitute an important group amongst the genetic causes of Parkinsonism at any age. The main IEM causing Parkinsonism are metal-storage diseases, neurotransmitter defects, lysosomal storage disorders and energy metabolism defects. IEM should not be neglected as many of them represent treatable causes of Parkinsonism. Here we review IEMs causing this neurological syndrome and propose diagnostic approaches depending on the age of onset and the associated clinical and neuroimaging features.     

Modelling inborn errors of metabolism in zebrafish

The majority of human inborn errors of metabolism are fatal multisystem disorders that lack proper treatment and have a poorly understood mechanistic basis. Novel technologies are required to address this issue, and the use of zebrafish to model these diseases is an emerging field. Here we present the published zebrafish models of inborn metabolic diseases, discuss their validity, and review the novel mechanistic insights that they have provided. We also review the available methods for creating and studying zebrafish disease models, advantages and disadvantages of using this model organism, and successful examples of the use of zebrafish for drug discovery and development. Using a zebrafish to model inborn errors of metabolism in vivo, although still in its infancy, shows promise for a deeper understanding of disease pathomechanisms, onset, and progression, and also for the development of specific therapies.     

Flux analysis of inborn errors of metabolism

Patients with an inborn error of metabolism (IEM) are deficient of an enzyme involved in metabolism, and as a consequence metabolism reprograms itself to reach a new steady state. This new steady state underlies the clinical phenotype associated with the deficiency. Hence, we need to know the flux of metabolites through the different metabolic pathways in this new steady state of the reprogrammed metabolism. Stable isotope technology is best suited to study this. In this review the progress made in characterizing the altered metabolism will be presented. Studies done in patients to estimate the residual flux through the metabolic pathway affected by enzyme deficiencies will be discussed. After this, studies done in model systems will be reviewed. The focus will be on glycogen storage disease type I, medium-chain acyl-CoA dehydrogenase deficiency, propionic and methylmalonic aciduria, urea cycle defects, phenylketonuria, and combined D,L-2-hydroxyglutaric aciduria. Finally, new developments are discussed, which allow the tracing of metabolic reprogramming in IEM on a genome-wide scale. In conclusion, the outlook for flux analysis of metabolic derangement in IEMs looks promising.