遗传代谢病枫糖尿症研究进展

doi:10.11852/zgetbjzz2017-25-02-10

摘要/Abstract

摘要： 枫糖尿症(MSUD)是由于支链氨基酸及其衍生的α-酮异已酸、α-酮异戊酸等在血和脑脊液中蓄积,间接地抑制α-羟酸的分解,致使α-羟丁酸和α-羟异戊酸在患儿的尿和汗液中大量排泄,形成特异焦糖味而被称之为“枫糖尿症”。如果MSUD不能及时治疗将导致癫痫发作、昏迷、甚至死亡。本文对MSUD的发病机制,临床诊断及治疗研究进展进行综述。

关键词: 枫糖尿症, 支链氨基酸, 遗传学, 诊断, 治疗, 新生儿筛查

Abstract: Maple syrup urine disease (MSUD) is an inherited disorder of branched chain amino acids and their derivatives including alpha ketoisocaproic acid (KICA),alpha-ketoisovaleric acid (KI-VA) and so on.The disorder inhibits indirectly the catabolism of alpha-hydroxy acids and Results in immense deposits of alpha hydroxy butyrate and a hydroxyl isovalerate in patient's urine and sweat which give rise to the classic "maple syrup" or burnt sugar smell.Acute elevations of branched chain amino acids and their derivatives cause metabolic encephalopathy,if no timely treatment of maple syrup urine disease will lead to seizures,coma and even death.The pathogenesis,clinical diagnosis and treatment of MSUD are reviewed in this paper.

Key words: maple syrup urine disease, branched chain amino acid, genetics, diagnosis, therapy, neonatal screening

中图分类号:

R179

宋东坡综述, 李文杰审校. 遗传代谢病枫糖尿症研究进展[J]. 中国儿童保健杂志, 2017, 25(2): 143-146.

SONG Dong-po,LI Wen-jie. Research on metabolic disorder of maple syrup urine disease[J]. journal1, 2017, 25(2): 143-146.

参考文献

[1] Strauss KA,Morton DH.Branched-chain ketoacyl dehydrogenase deficiency:maple syrup disease[J].Curr Treat Options Neurol,2003,5(4):329-341.
[2] 惠秦,谷为岳,侯新琳,等,新生儿枫糖尿症1例[J].中国循证儿科杂志,2014,9(1):64-67.
[3] Strauss KA,Bridget W,Donna R,et al.Classical maple syrup urine disease and brain development:Principles of management and formula design[J].Mol Genet Metab,2010,99(4):333-345.
[4] Oyarzabal A,Martinez-Pardo M,Merinero B,et al.A Novel regulatorydefect in the branched-chain alpha-ketoacid dehydrogenasecomplex due to a mutation in the PPM1K gene causes a mild variantphenotype of maple syrup urine disease[J].Hum Mutat,2012,34(2):355-362.
[5] Gupta D,Bijarnia-Mahay S,Saxena R,et al.Identification of mutations,genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients[J].Eur J Med Genet,2015,58(9):471-478.
[6] Nellis MM,Danner DJ.Gene preference in maple syrup urine disease[J].Am J Hum Genet,2001,68(1):232-237.
[7] Zinnanti WJ,Lazoric J,Griffin K,et al.Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease[J].Brain,2009,132(pt4):903-918.
[8] Emilieu RM,Gregory JM,Scott CB,et al.Biochemical correlates off neuropsychiatric illness in maple syrup urine disease[J].J Clin Invest,2013,123(4):1809-1820.
[9] Yang N,Han LS,Ye J,et al.Clinical characteristics and analysis of mass spectrometric data in 33 patients with maple syrup urine disease[J].Zhonghua Yi Xue Za Zhi,2012,92(40):2839-2842.
[10] Couce ML,Ramos F,Bueno MA,et al.Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis[J].Eur J Paediatr Neurol,2015,19(6):652-659.
[11] Schadewaldt P,Bodner-Leidecker A,Hammen HW,et al.Significance of L-alloisoleucine in plasma for diagnosis of maple syrup urine disease[J].Clin Chem,1999,45(10):1734-1740.
[12] Kevin AS,Bridget W,Donna R,et al.Classical maple syrup urine disease and brain develogment:Principles of management and formula design[J].Mol Genet Metab,2010,99(4):333-345.
[13] Homanics GE,Skvorak K,Ferguson C,et al.Production and characterization of murine models of classic and intermediate maple syrup urine disease[J].BMC Med Genet,2006,7(2):33.
[14] Indiran V,Gunaseelan RE.Neuroradiological findings in maple syrup urine disease[J].J Pediatr Neurosci,2013,8(1):31-33.
[15] Atwal PS,Macmurdo C,Grimm PC.Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease[J].Mol Genet Metab Rep,2015,4(5):46-48.
[16] William JZ,Jelena L,Kathleen G,et al.Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease[J].Brain,2009,132(4):903-918.
[17] Chin HL,Aw MM,Quak SH,et al.Two consecutive partial liver transplants in a patient with classic maple syrup urine disease[J].Mol Genet Metab Rep,2015,4(1):49-52.
[18] Mazariegos GV,Morton DH,Sindhi R.Liver transplantation for classical maple syrup urine disease:long-term follow-up in 37 patients and comparative united network for organ sharing experience[J].J Pediatr,2012,160(1):116-121.
[19] Kristen JS,Kenneth D,Fabio M,et al.Placental stem cell correction of murine intermediate maple syrup urine disease[J].Hepatology,2013,57(3):1017-1023.
[20] Homanics GE,Skvorak K,Ferguson C,et al.Phenylbutyrate therapy for maple syrup urine disease[J].Hum Mol Genet,2011,20(4):631-640.
[21] Yang N,Han L,Gu X,et al.Analysis of gene mutations in Chinese patients with maple syrup urine disease[J].Mol Genet Metab,2012,106(4):412-418.