甲基丙二酸血症合并同型半胱氨酸尿症患者治疗效果分析

甲基丙二酸血症合并同型半胱氨酸尿症患者治疗效果分析

黄倬;顾学范;韩连书;叶军;邱文娟;张惠文;高晓岚;王瑜;季文君;李晓燕

【期刊名称】《中华儿科杂志》 【年(卷),期】2013(051)003

【摘要】Objective Combined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China.Patients with this disease can progress to death without timely and effective treatment.This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria.Method From September 2004 to April 2012,58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital.Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases.Their age when they were diagnosed ranged from 18 days to 30.8 years.The other 8 cases were from newborn screening.All the patients were treated with vitamin B12,betaine,folic acid,vitamin B6,and Lcarnitine.The physical and neuropsychological development,general laboratory

tests,the

levels

of

amino

acids,acylcarnitines,and

homocysteine in blood,and organic acids in urine were followed up.Result The follow-up period ranged from 1 month to 7.1 years.Three cases died (all were early-onset cases).In the other patients after treatment,the

symptoms

such

as

recurrent

vomiting,seizures,lethargy,and poor feeding disappeared,muscle

strength and muscle tension were improved,and general biochemical abnormalities such as anemia and metabolic acidosis were corrected.Among the surviving 55 cases,49 had neurological impairments such as developmental delay and mental retardation.The median levels of blood propionylcarnitine and its ratio with acetylcarnitine,serum homocysteine,and urine methylmalonic acid were significantly decreased (P ＜0.01),from 7.73 μmol/L (ranged from 1.5 to 18.61 μmol/L),0.74 (ranged from 0.29 to 2.06),97.3 μmol/L (ranged from 25.1 to 250 μmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 μmol/L (ranged from 0.47 to 12.09 μmol/L),0.16 (ranged from 0.03 to 0.62),43.8 μmol/L (ranged from 17 to 97.8 μmol/L) and

6.81

(ranged

from

0

to with

95.43)after combined

treatment,respectively.Conclusion Patients

methylmalonic acidemia and homocystinuria respond to a combined treatment

consisting

of

supplementation

of

hydroxycobalamin,betaine,folic acid,vitamin B6 and L-carnitine with clinical and biochemical improvement.But the long-term outcomes are unsatisfactory,with neurological sequelae in most patients.%目的 分析甲基丙二酸血症合并同型半胱氨酸尿症患者的治疗效果.方法 甲基丙二酸血症合并同型半胱氨酸尿症患者58例,男34例,女24例,其中临床患者50例(早发型42例,迟发型8例),首诊年龄18 d～30.8岁,新生儿筛查8例.治疗方法包括维生素

B12、甜菜碱、叶酸、维生素B6及左旋肉碱等.随访内容包括发育情况、常规实验室检测、血氨基酸、酰基肉碱、同型半胱氨酸及尿有机酸水平等.结果 58例患者治疗随访1个月～7.1年,其中死亡3例(早发型患者),其余患者治疗后急性期临床表现及常规生化异常基本恢复正常,其中49例留有不同程度运动语言及智力落后.患者血丙酰肉碱、丙酰肉碱与乙酰肉碱比值、同型半胱氨酸及尿甲基丙二酸水平中位数由治疗前的7.73 μmol/L、0.74、97.3 μmol/L及168.55降至随访时的2.74 μmol/L、0.16、43.8 μmol/L及6.81,差异均有统计学意义(Z=6.345、6.624、5.246、6.624,P均＜0.01).结论 甲基丙二酸血症合并同型半胱氨酸尿症患者经羟钴胺及其他药物综合治疗后,临床表现及血尿生化异常显著改善,但多数患者仍有运动语言及智力落后. 【总页数】5页(194-198)

【关键词】甲基丙二酸血症;甲基丙二酸;同型半胱氨酸;羟钴胺;治疗

【作者】黄倬;顾学范;韩连书;叶军;邱文娟;张惠文;高晓岚;王瑜;季文君;李晓燕 【作者单位】200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代谢病研究室;200092 上海交通大学医学院附属新华医院市儿科医学研究所内分泌遗传代