高氨血症患儿102例尿液气相色谱-质谱分析

Analysis of Urine Gas Chromatography-Mass Spectrometry in 102 Children with Hyperammoniemia

目的探讨气相色谱-质谱联用(GC-MS)分析方法在高氨血症病因诊断中的应用价值。方法采集2003年10月-2008年3月在广州市儿童医院儿内科住院的102例高氨血症患儿治疗前和30例健康对照组儿童尿液标本,分别进行尿液GC-MS检测,对尿中检出异常代谢产物的患儿进行血浆氨基酸分析,为进一步鉴别诊断,7例患儿接受了基因突变分析。结果102例中30例(29.4%)患儿尿GC-MS分析检出特殊异常代谢产物,其中10例患儿尿液中检出大量乳清酸、尿嘧啶;7例患儿尿液中检出大量半乳糖醇、半乳糖酸、半乳糖、4-羟基苯乙酸、4-羟基苯乳酸;4例患儿尿液中检出大量甲基丙二酸、甲基枸橼酸;6例患儿尿液中检出大量3-羟基丙酸、丙酰甘氨酸、2-甲基-3-羟基异戊酸、甲基枸橼酸;3例患儿尿液中检出大量3-甲基巴豆酰甘氨酸、甲基枸橼酸、3-羟基异戊酸、二羧酸。结合临床症状体征、血浆氨基酸分析和基因突变分析,最后分别确诊为尿素循环障碍10例,Citrin缺陷导致的新生儿肝内胆汁淤积症7例,丙酸血症6例,甲基丙二酸血症4例,多种羧化酶缺乏症3例。30例健康对照组儿童尿液无1例检出异常代谢产物。结论应用GC-MS分析技术,对高氨血症等遗传代谢病的早期诊断、早期治疗及降低发病率和病死率等具有重要的作用。

Objective To explore the application value of the gas chromatography -mass spectrometry analysis（ GC -MS）in the diagno- sis of hyperammoniemia. Methods The urine samples were collected form 102 children with hyperammoniemia before treatment and 30 healthy children as the control group. The 102 patients were hospitalized at Guangzhou children＇s hospital during Oct. 2003 to Mar. 2008. GC - MS was carried out in the urine samples. Analysis of the plasma amino acid was carried out in children with abnormal metabolic products detected in the urine. For further differential diagnosis,7 patients received the analysis of gene mutation. Results Special abnormal metabolic products were detected in the urine of 30 cases （29.4%） out of the 102 cases. Large quantity of orotic acid and uracil were found in l0 cases. Large quantity of galactitol, galactonic acid, galactose ,4 - hydroxyphenylacetic acid ,4 - hydroxyphenyllactic acid were found in 7 cases. Large quantity of methylmalonic acid, methylcitric acid were found in 4 cases. Large quantity of 3 - hydroxypropanoic acid, propionylglycine, 2 - methyl - 3 - hydroxyisovaleric acid, methylcitric acid were found in 6 cases. Large quantity of 3 - methylcrotonylglycine, methylcitric acid, 3 - hydroxyisovaleric acid, dicarboxylic acid were found in 3 cases. Combined with clinical symptoms and signs ,the analysis of plasma amino acids and the analysis of gene mutation, 10 patients were finally confirmed with urea cycle disorder,7 cases with neonatal intrahepatic cholestasis caused by Citrin deficiency,6 cases with propionic acidemia,4 cases with methylmalonic acidemia, and 3 cases with multiple carboxylase deficiency. No abnormal metabolic product was detected in the urine of the 30 healthy children. Conclusions The application of GC - MS plays an important role in the early diagnosis and early treatment of hyperammoniemia, and lowering the incidence and mortality of inherited metabolic disease such as hyperammoniemia.