有机酸代谢病导致的猝死及危重症合并症

有机酸代谢病是一组由于三大物质代谢过程中某些酶缺陷导致羧基酸蓄积的疾病,亦是最常见的遗传代谢病之一。该类疾病临床特征缺乏特异性,在某些代谢压力下,可以急性发作,出现代谢性酸中毒、低血糖、高氨血症、急性脑病等危重症,甚至猝死。随着串联质谱及气相质谱技术的发展及新生儿遗传代谢病筛查的普及,有机酸代谢病越来越受到医疗工作者的关注。文章就有机酸代谢病与猝死及危重症的关系进行分析。     

猝死与遗传代谢病

猝死是指貌似健康的人,因潜在某种器质性疾病或功能障碍所引起的急速、意外的自然死亡。遗传代谢病是因维持机体正常代谢所必需的某种酶、运载蛋白、膜或受体等的编码基因突变而出现相应的病理和临床症状的一类疾病,其中有机酸代谢障碍、氨基酸代谢病、尿素循环障碍、糖代谢异常、脂质沉积病、线粒体病等均可导致猝死,共同特点为安定期无症状或仅有一些非特异性症状,在某种诱因刺激下急性发病,直接死因可能为低血糖、能量合成障碍、高氨血症、异常代谢产物的急性中毒、血管栓塞等。若治疗合理,患者可有效缓解。对于病因不明的濒死患者应保存尿、血标本或组织,以争取死亡后的诊断。     

19例危重症患儿遗传代谢病的临床分析

目的 进一步提高儿科医生对危重症患儿遗传代谢病的认识,从而提高其临床诊断率和治疗率,以挽救更多遗传代谢病患儿的生命,减少后遗症的发生.方法 2004年1月至2010年3月我院PICU收治的最终确诊为遗传代谢病患儿19例,回顾性分析19例患儿的发病年龄、首发症状、脏器损害类型和程度、合并症以及治疗转归情况.结果 19例患儿的平均发病年龄(5.94±6.52)个月,其中1岁以下的婴幼儿占79%.19例患儿中瓜氨酸血症3例,甲基丙二酸血症3例,酪氨酸血症2例,生物素缺乏症2例,糖原累积症2例,同型半胱氨酸血症2例,丙酸血症1例,枫糖尿病1例,高氨血症(鸟氨酸氨甲酰基转移酶缺乏症)1例,线粒体病1例,戊二酸血症1例.其中发生脏器功能衰竭的患儿11例(58%),包括呼吸衰竭7例、肝功能衰竭4例、心功能衰竭1例.代谢紊乱患儿共12例(63%),包括代谢性酸中毒10例,血乳酸增高7例,高血氨5例,低血糖2例.1例出现肾病综合征表现(5%).6例患儿(32%)心脏超声显示先天性心脏病(4例房间隔缺损,2例肥厚性心肌病).6例患儿(32%)头颅MRI检查提示存在不同程度的脑发育不良和脑白质病变.1例患儿(5%)腹部超声显示肝硬化.1例患儿(5%)的智力测试表明智力落后.结论 遗传代谢病临床首发表现往往缺乏特异性,甚至以重要器官功能衰竭或猝死样症状为临床首发表现.PICU中收治的遗传代谢病疑似患儿,应尽快获得患儿的血、尿标本进行生化检查、串联质谱及气相色谱质谱分析、酶活性检测,尽早确诊,为及时挽救危重症患儿的生命、减少后遗症创造条件.     

儿科内分泌遗传代谢疾病研究进展

2007年我国儿科内分泌遗传代谢病研究在基础和临床方面均较往年深入,一些新的诊断和治疗方法得以建立和应用,多中心临床和流行病学研究已经开展.对遗传病特别是代谢病的认识逐渐加深,全国多家医院已经开始致力酶学和基因诊断,并取得了初步成果.     

第八届全国内分泌遗传代谢病学术会议纪要

第八届全国儿科内分泌遗传代谢病学术会议于2004年10月11日至15日在成都举行。来自全国26个省、市和地区的214名代表出席了会议;大会共收到论文207篇,内容涉及性腺、糖尿病、甲状腺、垂体、肥胖和遗传代谢等疾病。会议邀请11位中、外专家进行了专题讲座,内容为：(1)从青春发育年龄提前的年代趋势解析至对女性性早熟的再认识;(2)遗传代谢性疾病的治疗;     

新生儿串联质谱遗传代谢病筛查结果判读

遗传代谢病是由于基因缺陷导致体内某些物质代谢障碍,病种繁多,可累及多系统,临床表现无特异性。如未早期诊断和干预,总体预后差。串联质谱可检测血中的氨基酸和肉碱,是诊断氨基酸、有机酸、脂肪酸代谢病的有效手段,近年来被越来越广泛地应用于新生儿疾病筛查,大大有利于遗传代谢病的早期诊断。文章对新生儿串联质谱遗传代谢病筛查结果的判读进行介绍。     

PICU十例危重遗传代谢病临床分析

目的 进一步提高PICU儿科医生对危重症遗传代谢病患儿的认识,以提高其临床诊断率、治疗率,减少后遗症发生.方法 2014年3月至2017年1月我院PICU收治10例诊断为遗传代谢病的患儿,回顾性分析10例患儿的发病年龄、起病特点、临床表现、脏器损害类型和程度、合并症以及治疗转归情况.结果 10例患儿的发病年龄中位数为5.5个月,其中l岁以下婴幼儿6例.10例患儿中,甲基丙二酸血症2例,尿素循环障碍2例,鸟氨酸氨甲酰转移酶缺乏症1例,苯丙酮尿症1例,生物素和生物素酶缺乏1例,尼曼匹克病1例,线粒体脑肌病1例,神经元蜡样脂褐质沉积症1例.6例患儿发生脏器功能衰竭,其中4例均为多脏器功能衰竭,包括呼吸衰竭4例、肝功能衰竭2例、心力衰竭2例、肾功能衰竭2例.8例代谢紊乱患儿,包括代谢性酸中毒5例,低血糖症5例,高血糖症1例,高氨血症4例,离子紊乱4例,高乳酸血症2例.合并重症感染4例,3例为重症肺炎,1例合并脓毒症.1例患儿心脏超声示右心大,原发性肺动脉高压合并心包少量积液,同时其肺CT可见双肺弥漫性病变,腹部B超提示肝脾肿大.3例患儿头颅MRI提示存在不同程度的双侧大脑对称性异常信号.结论 遗传代谢病种类繁多,发病早,起病急,临床表现缺乏特异性,甚至以重要器官功能衰竭或猝死样症状为首发表现,PICU医生需要警惕不要遗漏遗传代谢病.对PICU中收治的遗传代谢病疑似患儿,应尽快获得有效的血、尿标本进行生化检查、串联质谱及气相色谱质谱分析、酶活性检测,以及必要时的基因检测,骨髓穿刺等相应检查,尽早确诊,以便及时挽救危重症患儿的生命、减少后遗症、判断患儿的预后.     

儿童内分泌遗传代谢疾病临床研究进展

2008年我国儿科内分泌遗传代谢病领域共发表论文140余篇,其中内分泌疾病近百篇,内容涉及肥胖病、中枢性性早熟、宫内发育迟缓、矮小以及性发育和性分化等.遗传代谢病共40余篇,内容涉及苯丙酮尿症、黏多糖贮积症、肝豆状核变性以及一些少见代谢性疾病,同时还涉及一些遗传代谢病的诊断和产前诊断方法的建立和应用.2008年11月,第5届亚太儿童内分泌学会学术会议在韩国首尔举行,50余篇中国学者的优秀论文参加了交流.本文主要介绍2008年国内儿童内分泌遗传代谢病临床研究领域的进展.     

全国儿科遗传代谢、内分泌疾病诊疗新进展学习班通知

随着疾病谱的改变,儿童遗传代谢和内分泌疾病日益引起重视。为加快我国儿科遗传代谢内分泌疾病专业的发展,提高对相关疾病的诊疗水平,促进学科间的交流与合作,经国家继续医学教育委员会批准,定于2010年第2季度在武汉举办全国“儿科遗传代谢、内分泌疾病诊疗新进展”学习班[2010-06-01-048（国）]。     

新生儿遗传代谢病筛查阳性及确诊患者的管理

新生儿遗传代谢病筛查是出生缺陷防控的第三级防御措施,随着我国各地筛查率不断提高,如何提高筛查阳性召回率及保证确诊患儿规范管理的问题突显。文章将针对筛查阳性及确诊病例管理中可能存在的诸多难点提出建议对策,旨在进一步提高我国新生儿遗传代谢病规范筛诊治质量,真正体现新生儿疾病筛查与诊治并重。     

糖代谢异常与猝死及危重症

碳水化合物是机体内重要的能量来源,包括葡萄糖、半乳糖、果糖和糖原。先天性酶的缺陷会引起多种糖代谢异常, 其中多数疾患可导致低血糖, 大部分呈慢性经过, 但部分严重的糖代谢异常如糖原累积病Ⅰ型、 果糖-1, 6-二磷酸酶缺乏症等, 患者可急性起病, 病情危重导致低血糖性脑病、 心肌病、 肝病、 骨骼肌损害等多器官疾病。若能及时诊断和干预, 大多糖代谢异常预后良好。一些严重患者猝死, 需要依靠代谢尸检明确病因诊断, 以指导家族遗传咨询。     

线粒体脂肪酸氧化代谢病与猝死

线粒体脂肪酸β氧化代谢病是一类潜在的致死性疾病。由于编码某种酶的基因致病突变导致酶活性缺乏,引起能量代谢衰竭和多器官损害。患儿临床表现复杂,轻重不同,可急可缓。少数既往无症状的患儿急性发病,在不明原因情况下发生心源性猝死。随着生化分析技术及基因检测技术的发展和应用,通过对猝死患者的代谢尸检及基因分析,明确了线粒体脂肪酸β氧化代谢病是导致猝死的一组遗传病。通过串联质谱法扩展新生儿筛查或高危筛查,患儿可在无症状时期或疾病早期获得诊断,早期干预是减少残障及病死率的关键。     

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??Abstract??In recent years?? the significant progress has been made in the clinical diagnosis and treatment of inherited metabolic diseases. The molecular mechanism and pathophysiology of the diseases have been widely studied. Genetic counseling and prenatal diagnosis play an indispensable role in understanding occurrence and preventing recurrence of genetic diseases. This article is willing to present the related contents of genetic counseling and prenatal diagnosis.     

造血干细胞移植在遗传代谢病治疗中的应用

随着生化检测技术的进步和引进,我国儿童遗传代谢病检出率明显提高,随之而来更大的挑战是治疗问题。迄今已发现的500余种遗传代谢病中,多数疾病缺乏有效治疗方法,只能进行对症治疗,部分疾病通过传统的饮食、药物治疗能够得到控制,少数疾病可以进行酶替代疗法,如:Fabry病、戈谢病。为解决患者的长期治疗,细胞移植和基因治疗已成为现代研究的主流方向。从理论上讲,基因治疗是遗传代谢病的根本治疗方法,但既往Gaucher病和Hunter病基因治疗研究结果显示,未能改善患儿生化与临床表现,技术方面也存在很多短期内难以突破的困难,如:基因转染率、适…     

Scoring approaches to the recognition of cases of sudden infant death syndrome

The aim of this study was to create a scoring method to distinguish between sudden infant death syndrome (SIDS) and cases of sudden death resulting from life-threatening conditions (LTC). Four hundred infants less than one year old who died suddenly out of hospital in St Petersburg between 1983 and 1990 and who underwent a complete autopsy, were entered into the study. In 200 cases, the main diagnosis was SIDS, while in the remaining 200 cases, death was interpreted as resulting from LTC; 115 clinical and 240 morphological signs and symptoms were evaluated in each case. The statistical approach was based on the method of stepwise logistic regression analysis and it helped to identify 6 clinical and 12 morphological signs which, combined, made it possible to distinguish between SIDS and non-SIDS (LTC) cases most accurately.     

急诊患者遗传代谢病的快速识别与急救

遗传代谢病患者一旦急性发病,多陷于严重中毒、能量代偿不足、神经意识昏睡状态,诊断治疗不及时会导致严重的脑损伤或发育障碍,因此就诊时需要快速有效的代谢检测来明确诊断、决定治疗方案.急诊就诊30 min之内的紧急实验室一线检查结果是鉴别诊断和制定抢救治疗方案的重要参考依据,相继24 h内根据一线检查结果完善相应的遗传代谢病的二线实验室检查是明确诊断遗传代谢病和采取有效治疗方案的关键.     

Home monitoring for infants at risk of the sudden infant death syndrome

Abstract This study evaluates the effectiveness and social implications of home monitoring of 31 infants at risk of sudden infant death syndrome (SIDS). Thirteen siblings of children dying of SIDS, nine near miss SIDS infants and nine preterm infants with apnoea persisting beyond 40 weeks post conceptual age were monitored from a mean age of 15 days to a mean of 10 months. Chest movement detection monitors were used in 27 and thoracic impedance monitors in four. Genuine apnoeic episodes were reported by 21 families, and 13 infants required resuscitation. Apnoeic episodes occurred in all nine preterm infants but in only five (38%) of the siblings of SIDS (P<0.05). Troublesome false alarms were a major problem occurring with 61% of the infants and were more common with the preterm infants than the siblings of SIDS. All but two couples stated that the monitor decreased anxiety and improved their quality of life. Most parents accepted that the social restrictions imposed by the monitor were part of the caring process but four couples were highly resentful of the changes imposed on their lifestyle.
The monitors used were far from ideal with malfunction occurring in 17, necessitating replacement in six, repair in six and cessation of monitoring in three. The parents became ingenious in modifying the monitors to their own individual requirements
Although none of these 31 'at risk' infants died the study sample was far too small to conclude whether home monitoring prevented any cases of SIDS.     

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??Childhood and adolescence are key periods for bone development and mineralization. Bone diseases in childhood and adolescence can result in skeleton deformities, decreased adult height and changed peak bone mass. It would be very important to early diagnose and treat bone diseases in childhood and adolescence. According to the clinical manifestation, laboratory examinations and X-ray, bone diseases can be classified as metabolic bone disorders of calcium and phosphate, and genetic bone diseases. The pathogenesis, clinical manifestations, biochemical and radiological features of bone disease in childhood and adolescence were summarized. Progress in radiological examinations and treatment of these diseases were reviewed.     

The A985 to G mutation of the medium-chain acyl-CoA dehydrogenase gene and sudden infant death syndrome in Normandy

Medium-chain acyl-CoA dehydrogenase deficiency is the most common genetic defect of hepatic fatty acid oxidation. Clinical signs are somnolence and lethargy potentially leading to coma. Death occurs during the first attack in about 20% of cases, suggesting sudden infant death syndrome. A point mutation (adenine to guanine at position 985) in exon 11 of the medium-chain acyl-CoA dehydrogenase gene accounts for 90% of medium-chain acyl-CoA dehydrogenase deficiency-causing alleles. Such a high prevalence of a single mutation makes it possible to estimate the incidence of medium-chain acyl-CoA dehydrogenase deficiency in the general population and in sudden infant death syndrome. The study was performed by polymerase chain reaction amplification from blood spots on filter paper in 2000 randomly selected newborns (group I) and in 225 infants dead from sudden infant death syndrome (group II). Among 2000 newborns, 17 were found to be heterozygote for the G985 mutation. In group 11, one child was found with a single copy of the G985 mutation. So. the estimated frequency of the G985 mutation in the general population was 1/118 and the incidence of medium-chain acyl-CoA dehydrogenase deficiency was calculated as around 1/45 000 in Normandy.     

Has changing diagnostic preference been responsible for the recent fall in incidence of sudden infant death syndrome in South Australia?

Objective: An apparent decrease in deaths attributed to sudden infant death syndrome (SIDS) has been noted in a number of diverse geographical areas during the past several years. At the same time the definition of SIDS has been in a state of flux and some observers have raised the possibility that the fall in SIDS deaths is due to diagnostic transfer rather than to a genuine decrease in numbers. The present study was undertaken to investigate this possibility.
Methodology: All sudden and unexpected deaths in infants under 1 year of age in South Australia during a 10 year period from 1984 to 1993 were reviewed.
Results: The number of deaths due to SIDS fell from 40 in 1984 to 17 in 1993, with a maximum of 52 cases per year in 1987. In contrast, the number of cases of sudden death not due to SIDS remained under 10 per year. The overall infant death rate also fell, while the total number of births per year remained relatively unchanged.
Conclusions: The lack of major change in sudden infant death rates from other causes, combined with the fall in SIDS deaths, is not supportive of diagnostic transfer being a major determinant of the declining SIDS death rate. Therefore, other factors are likely to be responsible for the falling SIDS rate in this population.