高危新生儿遗传代谢病临床病因学分析

Study of clinic etiologies about newborn infants with high risk of inborn error of metabolism

目的初步研究新生儿重症监护室(NICU)先天性遗传代谢病(IEM)高危新生儿的临床病因学。方法应用气相色谱-质谱联用分析法(GC/MS)对100例临床IEM高危新生儿进行新鲜晨尿有机酸分析,并查血常规、肝肾功能、乳酸、丙酮酸、β-羟丁酸、血氨和同型半胱氨酸,其中24例患儿尿有机酸分析结果阳性,临床拟诊为IEM,对临床拟诊为IEM的24例患儿进行1～2个疗程的治疗,之后复查GC/MS尿有机酸分析。结果 24例临床拟诊为IEM的患儿12例确诊为IEM,其中丙酮酸血症、酪氨酸血症和同型半胱氨酸血症各2例,甲基丙二酸尿症、戊二酸血症Ⅱ型、乳糖不耐症、高甲硫氨酸血症、β-酮硫解酶缺乏症和鸟氨酸氨甲酰转移酶缺乏症各1例,均呈常染色体隐性遗传。12例IEM患儿的临床表现各不相同,其中血管病变3例(微血栓形成1例和脑实质内出血2例),新生儿惊厥和复发性代谢性酸中毒各2例,新生儿猝死、难治性低血糖、顽固性腹泻、遗传相关性高胆红素血症和重症肺炎各1例。12例IEM患儿的疾病极期,100%出现高氨血症,83%出现丙酮酸血症,67%出现肾损害和代谢性酸中毒,50%出现肝损害,42%出现血液系统损害。结论高危新生儿IEM临床病因复杂,随着新技术的发展,新生儿IEM疾病谱不断扩大,进一步揭示了高危新生儿病因,为临床诊治提供依据。

Objective To investigate the clinic etiologies about newborn infants with high risk of inborn error of metabolism（IEM） in NICU.Methods We did a urine organic acid analysis about 100 newborn infants with high risk of IEM by GC/MS.At the same time,blood routine,liver and renal function,blood lactic acid,blood pyruvic acid,β-hydroxybutyric acid,blood ammonia and serum homocysteine were determined.There were 24 patients diagnosed IEM by analysis results among the 100 cases.After 1 or 2 courses of treatment to the 24 patients,we did follow-up examination.Results There were 12 cases confirmed with IEM in the 24 patients,including 2 patients with propionic acidemia（PA）,2 with tyrosinemia,2 with homocystinemia,1 with methylmalonic aciduria（MMA）,1 with glutaric acidosis type II（GAII）,1 with congenital lactose intolerance,1 with hypermethioninemia,1 with β-ketothiolase deficiency and 1 with ornithine carbamoyltransferase deficiency （OCTD）.Those diseases were autosomal recessive inheritance.There were different clinical features in 12 IEM cases,including 3 patients with blood vessel pathological changes （microthrombus engendered and encephalon parenchyma haemo-rrhage）,2 with eclampsia,2 with recurred metabolic acidosis,1 with sudden death,1 with recurred hypoglycemia,1 with obstinated diarrhoea,1 with jaundice correlated with inheritance and 1 with severe pneumonia.In the crises of the 12 IEM patients,100% patients showed hyperammonemia,83% metabolic acidosis and pyruvemia,67% nephridium impaired,50% with liver impaired,42% with blood impaired.Conclusions The newborn infants with high risk of IEM had complicated etiologies.The neonates＇ IEM spectrum were amplification by new technique（eg.GC/MS）.The amplification of IEM spectrum would show more etiologies of newborn and help diagnosis and treatment.