甲基丙二酸血症.docVIP

甲基丙二酸血症诊治研究进展 上海市儿科医学研究所，内分泌遗传代谢病研究室，上海200092） 上海新华医院小儿内科韩连书 摘要： 甲基丙二酸血症是一种常见的有机酸血症，属于常染色体隐性遗传，临床表现无特异性，以呕吐、嗜睡等神经系统症状为主。诊断依靠串联质谱检测血中的酰基肉碱和气相质谱检测尿甲基丙二酸。对伴有同型半胱氨酸血症患儿，治疗以维生素B12、甜菜碱和左旋肉碱为主；对不伴有同型半胱氨酸血症患儿以限制天然蛋白质摄入，给予去除异亮氨酸、缬氨酸、甲硫氨酸和苏氨酸的特殊奶粉及左旋肉碱治疗为主。维生素B12治疗有效型预后较好，维生素B12治疗无效型预后较差。 关键词： 甲基丙二酸血症；诊断；治疗 Progress of Diagnosis and Therapy in Methylmalonic Acidemia WANG Fei , HAN Lian-shu (Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medical, Shanghai 200092, China) Abstract： Methylmalonic acidemia is an autosomal recessive organic acidemia, which is charactered by various presentations, especially the neurological symptoms such as vomiting, lethargy and so on. The diagnosis of this disease depends on the measurement of acylcarnitine in the blood by gas-chromatography mass spectrometry and the detection of methylmalonic acid in the urine by tandem mass spectrometry. The patients with methylmalonic acidemia and homocystinuria should be mainly treated with vitamin B12, betaine and L-carnitine, while the patients with isolated methymalonic acidemia should be treated with protein restriction, the special milk formula without isoleucine, valine, methionine, and threonine, and be given L-carnitine. Compared with the vitamin B12-nonresponsive patients, the vitamin B12-responsive ones have better outcome. Key words： methylmalonic acidemia；diagnosis；treatment  甲基丙二酸血症（methylmalonic acidemia, MMA）是一种常见的有机酸血症，属于常染色体隐性遗传病。主要是由于甲基丙二酰辅酶A变位酶（methylmalonyl-CoA mutase, MCM）或其辅酶钴胺素代谢缺陷所致。1967年，Oberholzer和Stokke分别报道了首例MMA患者。其患病率美国为1：48,000；意大利患病率为1：115,000；德国为1：169,000[1]；日本为1：50,000。国内患病率尚不清楚，但对临床疑似患儿进行串联质谱检测发现，甲基丙二酸血症患儿并不少见[2,3]，为此对MMA近几年诊治研究进展进行探讨，以助于提高儿科医生对本病的认识，使更多的患儿得到及时诊断和治疗。 1 甲基丙二酸血症病因及分型 甲基丙二酸是异亮氨酸、缬氨酸、甲硫氨酸、苏氨酸、胆固醇和奇数链脂肪酸分解代谢途径中甲基丙二酰辅酶A的代谢产物，正常情况下在MCM及AdoCbl的作用下转化生成琥珀酸，参与三羧酸循环。MCM缺陷或AdoCbl代谢障碍导致甲基丙二酸、丙酸、甲基枸橼酸等代谢物异常蓄积，引起神经、肝脏、肾脏、骨髓等多脏器损伤[4]。