甲基丙二酸血症是先天性有机酸代谢异常中最常见的疾病,为常染色体隐性遗传,临床表现无特异性,以喂养困难、反复呕吐及嗜睡、惊厥、运动障碍等神经系统症状为主。诊断依靠串联质谱检测血酰基肉碱和气相色谱-质谱检测尿甲基丙二酸。维生素B12治疗有效并伴有同型半胱氨酸血症的患儿,治疗以维生素B12、左旋肉碱和甜菜碱为主,预后较好;维生素B12治疗无效型患儿,给予去除异亮氨酸、缬氨酸、苏氨酸和蛋氨酸的特殊配方奶粉及左旋肉碱治疗为主,预后较差。
Abstract
Methylmalonic acidosis is the most common disease of congenital organic acid metabolic disorders,and it is an autosomal recessive disease.The cinical manifestations of Methylmalonic acidosis is no specific.It is characterized by feeding difficulties,recurrent vomiting and the neurological symptoms such as lethargy,convulsion,movement disorders,and so on.Diagnosis of the disease depends on the measurement of acylcarnitines in the blood by tandem mass spectrometry and the detection of methylmalonic acid in the urine by gas-chromatography mass spectrometry.The vitamin B12-responsive patients with methylmalonic acidemia and homocystinuria should be mainly treated with vitamin B12,L-carnitine and betaine,while the vitamin B12-nonresponsive patients should be treated with protein restriction,the special milk formula without isoleucine,valine,threonine and methionine,as well as the L-carnitine.Compared with the vitamin B12-nonresponsive patients,the vitamin B12-responsive ones have better outcome.
关键词
甲基丙二酸血症 /
诊断 /
治疗
Key words
Methylmalonic acidemia /
diagnosis /
treatment
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参考文献
[1] Tu WJ.Methylmalonic acidemia in mainland China[J].Ann Nutr Metab,2011,58(4):281.
[2] Liu MY,Liu TT,Yang YL,et al.Mutation profile of the MUT gene in Chinese methylmalonic aciduria patients[J].JIMD Rep,2012,6:55-64.
[3] Illson ML,Dempsey-Nunez L,Kent J,et al.High resolution melting analysis of the MMAB gene in cblB patients and in those with undiagnosed methylmalonic aciduria[J].Mol Genet Metab,2013,110(1-2):86-89.
[4] Vatanavicharn N,Champattanachai V,Liammongkolkul S,et al.Clinical and molecular findings in Thai patients with isolated methylmalonic acidemia[J].Mol Genet Metab,2012,106(4):424-429.
[5] Brasil S,Richard E,Jorge-Finnigan A,et al.Methylmalonic aciduria cblB type:characterization of two novel mutations and mitochondrial dysfunction studies[J].Clin Genet,2015,87(6):576-581.
[6] Joseph J,Loscalzo J.Methoxistasis:integrating the roles of homocysteine and folic acid in cardiovascular pathobiology[J].Nutrients,2013,5(8):3235-3256.
[7] Wang X,Sun W,Yang Y,et al.A clinical and gene analysis of late-onset combined methylmalonic aciduria and homocystinuria,cblC type,in China[J].J Neurol Sci,2012,318(1-2):155-159.
[8] 刘玉鹏,杨艳玲.甲基丙二酸尿症cblC 型合并同型半胱氨酸血症的临床与实验室研究进展[J].中华儿科杂志,2013,51(4):313-316.
[9] Gündüz M,Ekici F,Ozaydin E,et al.Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C disease due to a novel mutation in the MMACHC gene[J].Eur J Pediatr,2014,173(12):1707-1710.
[10] Fischer S,Huemer M,Baumgartner M,et al.Clinical presentation and outcome in a series of 88 patients with the cblC defect[J].J Inherit Metab Dis,2014,37(5):831-840.
[11] Cornec-Le GE,Delmas Y,De Parscau L,et al.Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency[J].Am J Kidney Dis,2014,63(1):119-123.
[12] Huemer M,Scholl-Burgi S,Hadaya K,et al.Three new cases of late-onset cblC defect and review of the literature illustrating when to consider inborn errors of metabolism beyond infancy[J].Orphanet J Rare Diseases,2014,9:161.
[13] Martinelli D,Deodato F,Dionisi-Vici C.Cobalamin C defect:natural history,pathophysiology,and treatment[J].J Inherit Metab Dis,2011,34(1):127-135.
[14] 毋盛楠,韩连书,叶军,等.甲基丙二酸血症患者血串联质谱及尿气相色谱质谱检测分析[J].中华医学杂志,2013,93(8):561-565.
[15] Matos IV,Castejón E,Meavilla S.Clinical and biochemical outcome after hydroxocobalamin dose escalation in a series of patients with cobalamin C deficiency[J].Mol Genet Metab,2013,109(4):360-365.
[16] Pastore A,Martinelli D,Piemonte F.Glutathione metabolism in cobalamin deficiency type C (cblC)[J].J Inherit Metab Dis,2014,37(1):125-129.
[17] Chen PW,Hwu WL,Ho MC,et a1.Stabilization of blood methylmalonic acid level in methylmalonic acidemia after liver transplantation[J].Pcdiatr Transplant,2010,14(3):337-341.
[18] 刘玉鹏,马艳艳,杨艳玲,等.早发型甲基丙二酸尿症 160例新生儿期异常表现[J].中华儿科杂志,2012,50(6):410-414.
[19] Tu WJ,Chen H,He J.Methylmalonic aciduria:newborn screening in mainland China[J].J Pediatr Endocrinol Metab,2013,26(3-4):399-400.
[20] Ribeiro LR,Della-Pace ID,de Oliveira Ferreira AP,et al.Chronic administration of methylmalonate on young rats alters neuroinflammatory markers and spatial memory[J].Immunobiology,2013,218(9):1175-1183.
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