組氨酸血癥ppt課件

1、組氨酸血癥(Histidinemia),,化學名：α-氨基-β-咪唑基丙酸英文名稱：histidine英文縮寫：His組氨酸是生長發(fā)育快速的嬰、幼兒期必需的氨基酸，其每日需要量約為35mg/kg,概念： Histidemia, first described by Ghadimi in 1961, is caused by a defect in histidase. The defect results in

2、 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

3、(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 decr

4、eased 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 (

5、Japan) to 1 in 37,000 (Sweden). Histidinemia is inherited as an autosomal recessive trait.,病因和發(fā)病機制,組氨酸的降解是通過尿刊酸階段轉(zhuǎn)變成谷氨酸，由組氨酸酶、尿刊酸酶、咪唑啉酮丙酸水解酶。組氨酸酶存在于肝細胞和皮膚組織中，尿刊酸酶僅限于肝細胞內(nèi)，前者缺乏時造成組氨酸血癥，后者缺乏時則導致尿刊酸尿癥組氨酸酶的碥碼基因(HAL)位于12q2

6、2～q24.1，該片段的缺失是導致組氨酸血癥的主要原因，有少數(shù)患者亦可能是由于基因21外顯子突變所造成的。組氨酸血癥是比較多見的一種常染色體隱性遺傳性代謝缺陷，對2000萬新生兒群體篩查的資料表明本病的發(fā)病率為1/11000。,組氨酸血癥患者組氨酸酶缺陷，一方面造成生理情況下組氨酸脫氨生成尿刊酸的代謝途徑受阻，引起組氨酸積聚，組氨酸濃度顯著升高，同時腦脊液組氨酸濃度也升高，尿中組氨酸的量增多；,,組氨酸酶,,組氨酸,尿刊酸,尿刊酸酶,亞

7、氨甲酰谷氨酸,,,,另一方面引起其他低效率代謝路徑的活躍，在各種替代途徑中，以組氨酸的轉(zhuǎn)氨、甲基化和乙酰化居多，但未發(fā)現(xiàn)組氨酸脫羧產(chǎn)物的增加。大量的組氨酸旁路代謝產(chǎn)物咪唑丙酮酸、咪唑乳酸和咪唑乳乙酸等從尿中排出。,尿中組氨酸的排出量為正常人的6-10倍，可高達27mmol/g肌酐。（正常<2mmol/g肌酐）；尿中除組氨酸外，排出咪唑丙酮酸、咪唑乳酸、咪唑乙酸等明顯增高，咪唑丙酮酸可使尿三氯化鐵反應陽性。血液和尿液組織中的尿刊

8、酸含量減少，常不能測出。腦脊液中組氨酸為48-142ummol/L,為正常值的3倍以上；,診斷和鑒別診斷,已經(jīng)報道的大多數(shù)病例是通過新生兒疾病篩查診斷的，患兒臨床表現(xiàn)的多樣化給臨床診斷帶來了一定的困難。測定血組氨酸濃度可以幫助診斷，血中組氨酸濃度與攝入蛋白質(zhì)的量有關(guān)。一般認為普通飲食時超過3.0mg/dl，禁食時大于2.5mg/dl應視為異常。采用毛細血管電泳質(zhì)譜儀直接分析尿標本的代謝產(chǎn)物，特異性和敏感性都比較好。尿液中組氨酸含量

9、增高和咪唑丙酮酸排出量增加；測定皮膚、肝臟的組氨酸酶活性可進一步確診。,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

10、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.

11、Application of this triad—stratum corneum epidermidis histidase determination, measurement of stratum corneum U/H, and analysis of excretion of histidine metabolites—should facilitate evaluation of the condition of infan