精氨酸血症的临床与分子遗传学研究进展

Advances in clinical and molecular genetics studies on argininemia

摘要:

精氨酸血症是一种罕见的尿素循环障碍性疾病，属常染色体隐性遗传，由于ARG1基因缺陷导致肝脏精氨酸酶缺乏，精氨酸降解障碍，鸟氨酸与尿素生成减少。本文就近年来精氨酸血症的临床表现、诊断、治疗、产前诊断与遗传学研究进展进行了综述。精氨酸血症患者临床表现复杂，缺乏特异性，诊断困难，常表现为痉挛性瘫痪、癫癎及小脑萎缩，早期常常被误诊为脑性瘫痪，生存质量极差，预后不良。血液氨基酸分析、精氨酸酶活性测定及基因分析是确诊精氨酸血症的重要方法。随着液相串联质谱技术在新生儿筛查和高危筛查中的应用，越来越多的精氨酸血症患者在无症状期或疾病早期获得诊断，通过低蛋白饮食、瓜氨酸与苯甲酸等药物治疗可改善预后。

Abstract:

Argininemia is a rare, autosomal recessive, metabolic disorder caused by an hereditary deficiency of hepatocytes arginase due to ARG1 gene defect. Arginase is the final enzyme in the urea cycle, catalyzing the hydrolysis of arginine to ornithine and urea. Research advances in the clinical manifestations, diagnosis, treatment, prenatal diagnosis and genetics of argininemia were reviewed in this paper. The clinical manifestations of patients with argininemia are complicated and nonspecific so that clinical diagnosis is usually difficult and delayed. Progressive spastic tetraplegia, seizures and cerebella atrophy are common clinical features of the disease. Blood amino acids analysis, arginase assay and ARG1 gene analysis are important to the diagnosis of argininemia. Early diagnosis and a protein-restricted diet with citrulline and benzoate supplements can contribute a lot to improve patient prognosis. With the application of liquid chromatography-tandem mass spectrometry in selective screening and newborn screening for inborn errors of metabolism, an ever-increasing number of patients with argininemia are detected at the asymptomatic or early stages.