戊二酸血症.ppt
戊二酸血症,Glutaric acidemia type I GA-I,电喷射串联质谱分析在不明原因死亡婴儿尸检血液标本酰基肉毒碱中的应用,背景：某些因先天性代谢性疾病死亡的婴儿在尸检后仍不能查明死因，可能被定义为婴儿猝死综合征。串联质谱分析可以揭示既往某些因脂肪酸氧化而死亡婴儿的死因。,方法：我们获得了来自美国及加拿大的7058份婴儿滤纸片血样本。通过串联质谱分析得到酰基肉毒碱及氨基酸的分析图谱，使用专门的方法分析其中的脂肪酸、有机酸、氨基酸代谢疾病。将尸检后血液样本与尸检胆汁样本、新生儿筛查血样本以及存在高危因素的大婴儿的血样本进行对比,结果：有66例标本提示存在代谢性疾病。主要疾病分别是：中链、极长链酰基辅酶A脱氢酶缺陷（分别是23例、9例），戊二酸血症I、II型（分别是3例、8例），肉碱转移酶缺陷（6例），严重肉碱缺乏（4例），异戊酸血症（4例）及长链羟酰辅酶A脱氢酶缺陷（4例）,结论：尸检的代谢筛查能够解释儿童死亡原因，以及提供儿童因遗传代谢死亡的可能数量。串联质谱对于尸检血样本的分析是非常有价值的，并应考虑作为检验人员及病理学家在调查儿童不明原因死亡时的常规检查方法,由以上可以证明儿童死亡后的血液标本对于先天性遗传代谢疾病的死因调查中的有效性,尸检血液标本,尸检胆汁标本,新生儿血液标本,高危儿血液标本,Increased glutaric acid was observed in several autopsy blood specimens. Significant increases in this metabolite are associated with the presumptive diagnosis of GA-I. 在某些尸检血样本中发现戊二酸增多，在这些代谢产物中如果戊二酸显著增多，提示存在戊二酸血症的可能,The acylcarnitine profile of a postmortem specimen identified from a patient with GA-I in which the metabolite C5DC is clearly increased is shown in Fig. 7A. 通过一个戊二酸血症病例尸检血样本的酰基肉碱图谱中可以看出， C5DC（glutarylcarnitine 戊二酰肉碱）是显著增高的,GA-I,We have presumptively identified 3 cases of GA-I in our 7058 analyses. The criteria for resumption of GA-I are based on the observation of an increased C5DC together with the lack of other increased acylcarnitines that may indicate other metabolic disorders, such as glutaric acidemia type II. 我们在7058份病例中推断假定存在3例戊二酸血症，假定病例的入选标准是C5DC的增高，同时没有另外的提示可能存在其他代谢疾病（如戊二酸血症II型）的酰基肉碱增高,GA-II，MADD,The median concentration of C5DC was 0.24mmol/L (Table 2) compared with control values of 0.09 mmol/L Other indices (LC, MC, SC), and both FC and TC were essentially the same as for controls. 病例中C5DC浓度的中位数是0.24mmol/L，而对比中的是0.09mmol/L，其他的指数（LC、MC、SC），以及游离酰基肉碱及总酰基肉碱基本均与对照组大致相同,戊二酸血症I型的诊断及治疗 修订推荐方案,Glutaric aciduria type I (synonym, glutaric cidemia type I) is a rare organic aciduria. Untreated patients characteristically develop dystonia during infancy resulting in a high morbidity and mortality. 戊二酸血症I型（又：戊二酸尿症I型）是少见的有机酸尿症。未经治疗的典型病例将发展为婴儿期肌张力减低，导致较高的病死率,The neuropathological correlate is striatal injury which results from encephalopathic crises precipitated by infectious diseases,immunizations and surgery during a finite period of brain development,or develops insidiously without clinically apparent crises. 神经病理学基础是：在脑发育某一阶段中，由于感染、免疫接种、手术所诱发的脑病危象对纹状体的损伤，或是隐袭性损伤而无脑病危象,Glutaric aciduria type I is caused by inherited deficiency of glutaryl-CoA dehydrogenase which is involved in the catabolic pathways of L-lysine, L-hydroxylysine and Ltryptophan. 戊二酸血症I型是由于先天性戊二酰-CoA脱氢酶（GCDH）缺乏引起，GCDH存在于L-赖氨酸、L-羟赖氨酸、L-色氨酸的代谢旁路中,This defect gives rise to elevated glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutarylcarnitine which can be detected by gas chromatography/mass spectrometry (organic acids) or tandem mass spectrometry(acylcarnitines). 这种缺陷可引起戊二酸、3-OH-戊二酸、戊烯二酸、戊二酰肉碱的增多，这些物质可通过气象色谱质谱分析（GC/MS 有机酸）及串联质谱分析（MS-MS 酰基肉毒碱）检验出,GA-I诊断路径,新生儿筛查,？已知突变的低排者,存在两种致病突变,C5DC截断值,排除GA-I,尿液分析测定GA 3-OH-GA,GA 3-OH-GA增高？,开始治疗,GCDH基因突变分析,GA-I 诊断成立,GCDH酶分析,GCDH活性减低或缺失,选择性筛查,可疑症状或体征,没有诊断可以推荐,
