Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency
Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency
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DOI：
10.1002/ajmg.c.30091
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发表时间：
2006-05-15
影响因子：
3.1
通讯作者：
Lee, B
中科院分区：
文献类型：
--
作者：
Scaglia, F;Lee, B
尿素循环由六个连续的酶反应组成，将废氮转化为尿素。尿素循环障碍是一组先天性肝脏代谢缺陷，常导致危及生命的高氨血症和高维生素A血症。已经描述了循环的所有酶的缺陷，并且尽管每种特定的病症导致不同前体的积累，但高氨血症和高维生素A血症是这些病症的常见生化标志。精氨酸酶是参与尿素循环最后一步的酶。它催化精氨酸转化为尿素和鸟氨酸。后者重新进入黑洞继续循环。高精氨酸血症是一种由精氨酸酶I缺陷引起的常染色体隐性疾病。与其他尿素循环障碍不同，这种情况通常与新生儿期的高氨血症性脑病无关。它通常在2至4岁的儿童期后期出现，主要表现为神经系统特征。如果不治疗，它会随着逐渐发育退化而进展。如果在病程早期进行饮食治疗和替代途径治疗，可以取得良好的结果。通过这种方法，可以防止神经系统进一步恶化，并部分恢复技能。通过新生儿筛查项目早期诊断这种疾病可能会导致更好的结果。这篇综述文章总结了这种疾病的临床特征，以及其生化，酶和分子特征。治疗，产前诊断和诊断通过新生儿筛查也进行了讨论。(c)2006 Wiley-Liss，Inc.
The urea cycle consists of six consecutive enzymatic reactions that convert waste nitrogen into urea. Urea cycle disorders are a group of inborn errors of hepatic metabolism that often result in life threatening hyperammonemia and hyperglutaminemia. Deficiencies of all of the enzymes of the cycle have been described and although each specific disorder results in the accumulation of different precursors, hyperammonemia and hyperglutaminemia are common biochemical hallmarks of these disorders. Arginase is the enzyme involved in the last step of the urea cycle. It catalyzes the conversion of arginine to urea and ornithine. The latter reenters the mitochondrion to continue the cycle. Hyperargininemia is an autosomal recessive disorder caused by a defect in the arginase I enzyme. Unlike other urea cycle disorders, this condition is not generally associated with a hyperammonemic encephalopathy in the neonatal period. It typically presents later in childhood between 2 and 4 years of age with predominantly neurological features. If untreated, it progresses with gradual developmental regression. A favorable outcome can be achieved if dietary treatment and alternative pathway therapy are instituted early in the disease course. With this approach, further neurological deterioration is prevented and partial recovery of skills ensues. Early diagnosis of this disorder through newborn screening programs may lead to a better outcome. This review article summarizes the clinical characterization of this disorder; as well as its biochemical, enzymatic, and molecular features. Treatment, prenatal diagnosis and diagnosis through newborn screening are also discussed. (c) 2006 Wiley-Liss, Inc.