甲基丙二酸尿症合并同型半胱氨酸血症57例临床分析

目的对57例甲基丙二酸尿症合并同型半胱氨酸血症患者进行回顾性研究。方法1996～2006年就诊的96例甲基丙二酸尿症患者中57例（59.4％）合并同型半胱氨酸血症,来自中国大陆16个省市,其中男32例,女25例,通过尿液、血液生化分析诊断,尿液有机酸测定采用GCMS分析技术,血清、尿液总同型半胱氨酸检测采用荧光偏振免疫测定法。结果57例患者尿中甲基丙二酸均显著增高,血清总同型半胱氨酸81.5～226.5μmol／L（正常对照4.5～12.4μmol／L）,尿液总同型半胱氨酸79.1～414.5μmol／L（正常对照1.0～20.0μmol／L）。其中13例（22.8％）于新生儿期发病,临床表现类似缺血缺氧性脑病;14例（24.6％）于1个月-1岁内发病,以神经系统损害为主要表现;9例（15.8％）于1岁～学龄前发病,以智力运动倒退为主要表现;18例（31.6％）于6～15岁发病,其中7例合并肝、肾、周围神经等多脏器损害。3例（5.3％）分别于16、24、34岁出现进行性智力运动倒退等异常。57例患者中11例（19.3％）死亡。46例（80.7％）接受维生素B12、叶酸、左旋肉碱、甜菜碱补充治疗,逐渐好转,11例（19.3％）完全康复。结论甲基丙二酸尿症合并同型半胱氨酸血症是中国人甲基丙二酸尿症的常见类型,患者个体差异大,可于新生儿期至成年各个时期发病,临床诊断困难。对于甲基丙二酸尿症患者应及早进行血浆、尿液总同型半胱氨酸测定,鉴别诊断,合理治疗。

Clinical studies on fifty-seven Chinese patients with combined methylmalonic aciduria and homocysteinemia

OBJECTIVE: Methylmalonic aciduria (MMA) is a common one of the congenital disorders of organic acids metabolism. Some of the patients with the disorder are complicated with homocysteinemia. Recently, gas chromatography-mass spectrometry (GCMS) has been used to diagnose MMA in China. However, the diagnosis of the patients with combined MMA and homocysteinemia is often delayed. In this study, the natural history, clinical features and outcome of 57 Chinese patients with combined MMA and homocysteinemia were investigated. METHODS: From 1996 to 2006, 96 MMA patients from 16 provinces or cities were diagnosed in our hospital by urine organic acids analysis using GCMS. Homocysteinemia was found by serum and urine total homocysteine determination using a fluorescence polarization immunoassay. RESULTS: Fifty-seven of the 96 MMA patients (59.4%, 32 males and 25 females) were found to have combined MMA and homocysteinemia. They had markedly increased urine methylmalonic acid, total serum homocysteine (81.5 to 226.5 micromol/L vs. normal range 4.5 to 12.4 micromol/L) and urine homocysteine (79.1 to 414.5 micromol/L vs. normal range 1.0 to 25.0 micromol/L). Thirteen (22.8%) of them presented with symptoms resembled hypoxic-ischemic encephalopathy in the neonatal period. Fourteen (24.6%) patients had the onset at the age of one month to 1 year with mental retardation, vomiting and epilepsy. Nine (15.8%) showed developmental delay, seizures, poor appetite or anemia from the age of 1 to 3 years. Eighteen (31.6%) had psycho-motor degeneration at the age of 6 to 15 years. Among them, 7 patients experienced multiple organ dysfunctions with liver dysfunction, hematuria, renal failure and peripheral neuropathy. Three (5.3%) patients developed progressive mental degeneration, motor disorders and anorexia at the ages of 16, 24 and 34 years. Eleven (19.3%) patients ultimately died; 5 (8.8%) of them were diagnosed postmortem. Forty-six (80.7%) patients were treated with vitamin B12, folic acid, L-carnitine and betaine supplementation and 11 (19.3%) of them recovered completely. CONCLUSIONS: Combined MMA with homocysteinemia is a common form of MMA in China. The clinical spectrum of the patients varies from severe neonatal-onset forms with high mortality to milder forms with adult-onset. Serum or urine total homocysteine analysis is important for the deferential diagnosis of the patients with MMA.