组氨酸血症ppt课件

组氨酸血症(Histidinemia),化学名：-氨基-咪唑基丙酸 英文名称：histidine 英文缩写：His 组氨酸是生长发育快速的婴、幼儿期必需的氨基酸，其每日需要量约为35mg/kg,概念： Histidemia, first described by Ghadimi in 1961, is caused by a defect in histidase. The defect results in elevated urinary excretion of histidine and its transamination products, and in high blood histidine. Blood histidine levels in histidinemic patients range from 290 to 1420 microM (normal 70-120 microM). Histidase (histidine ammonia-lyase, EC 4.3.1.3) catalyzes the deamination of L-histidine to trans-urocanic acid in the liver and skin of mammals. Histidase deficiency results in increased histidine and histamine in blood, and decreased urocanic acid in blood and skin. The clinical picture of histidinemia varies from complete normality to severe retardation, with many patients being asymptomaticFrequency of histidinemia ranges from 1 in 8000 (Japan) to 1 in 37,000 (Sweden). Histidinemia is inherited as an autosomal recessive trait.,病因和发病机制,组氨酸的降解是通过尿刊酸阶段转变成谷氨酸，由组氨酸酶、尿刊酸酶、咪唑啉酮丙酸水解酶。组氨酸酶存在于肝细胞和皮肤组织中，尿刊酸酶仅限于肝细胞内，前者缺乏时造成组氨酸血症，后者缺乏时则导致尿刊酸尿症 组氨酸酶的碥码基因(HAL)位于12q22q24.1，该片段的缺失是导致组氨酸血症的主要原因，有少数患者亦可能是由于基因21外显子突变所造成的。组氨酸血症是比较多见的一种常染色体隐性遗传性代谢缺陷，对2000万新生儿群体筛查的资料表明本病的发病率为1/11000。,组氨酸血症患者组氨酸酶缺陷，一方面造成生理情况下组氨酸脱氨生成尿刊酸的代谢途径受阻，引起组氨酸积聚，组氨酸浓度显著升高，同时脑脊液组氨酸浓度也升高，尿中组氨酸的量增多；,组氨酸酶,组氨酸,尿刊酸,尿刊酸酶,亚氨甲酰谷氨酸,另一方面引起其他低效率代谢路径的活跃，在各种替代途径中，以组氨酸的转氨、甲基化和乙酰化居多，但未发现组氨酸脱羧产物的增加。大量的组氨酸旁路代谢产物咪唑丙酮酸、咪唑乳酸和咪唑乳乙酸等从尿中排出。,尿中组氨酸的排出量为正常人的6-10倍，可高达27mmol/g肌酐。（正常2mmol/g肌酐）； 尿中除组氨酸外，排出咪唑丙酮酸、咪唑乳酸、咪唑乙酸等明显增高，咪唑丙酮酸可使尿三氯化铁反应阳性。 血液和尿液组织中的尿刊酸含量减少，常不能测出。 脑脊液中组氨酸为48-142ummol/L,为正常值的3倍以上；,诊断和鉴别诊断,已经报道的大多数病例是通过新生儿疾病筛查诊断的，患儿临床表现的多样化给临床诊断带来了一定的困难。 测定血组氨酸浓度可以帮助诊断，血中组氨酸浓度与摄入蛋白质的量有关。一般认为普通饮食时超过3.0mg/dl，禁食时大于2.5mg/dl应视为异常。采用毛细血管电泳质谱仪直接分析尿标本的代谢产物，特异性和敏感性都比较好。 尿液中组氨酸含量增高和咪唑丙酮酸排出量增加； 测定皮肤、肝脏的组氨酸酶活性可进一步确诊。,A highly specific and sensitive procedure for determining histidase activity, with labeled histidine as the substrate, that requires only 1 to 2 mg of stratum corneum epidermidis has been developed. Methods for determining ratios of urocanic acid to histidine (U/H) in stratum corneum epidermidis and for measuring excretion of histidine and its metabolites by thin-layer chromatography were developed. Application of this triadstratum corneum epidermidis histidase determination, measurement of stratum corneum U/H, and analysis of excretion of histidine metabolitesshould facilitate evaluation of the condition of infants and young children with