11例枫糖尿症患儿临床特征、代谢标志物及遗传异质性分析  

Clinical characteristics,biochemical metabolic biomarkers and genetic heterogeneity of 11 children with maple syrup urine disease

作　　者：王美仪 彭敏芝 邵咏贤 林云婷 蔡燕娜 徐佳南 刘丽 WANG Meiyi;PENG Minzhi;SHAO Yongxian;LIN Yunting;CAI Yanna;XU Jianan;LIU Li(Department of Genetics and Endocrinology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou,Guangdong 510623,P.R.China)

机构地区：[1]广州医科大学附属妇女儿童医疗中心遗传与内分泌科,广州510623

出　　处：《华西医学》2025年第1期23-28,共6页West China Medical Journal

基　　金：广东省自然科学基金-青年提升项目(2023A1515030248);广州市卫生健康委临床特色技术项目(2023C-TS60)。

摘　　要：目的总结分析枫糖尿症(maple syrup urine disease,MSUD)患儿的临床资料,以探讨MSUD的临床表型、生化标志物和遗传学相关性。方法回顾收集2011年1月—2016年10月11例就诊于广州医科大学附属妇女儿童医疗中心的MSUD患儿的临床资料,根据患儿临床表现和预后将患儿分为经典型组(n=6)和中间型/硫胺素有效型组(n=5),比较两组患儿生化代谢标志物的差异;同时对基因型和表型进行相关性分析。结果与中间型/硫胺素有效型组相比,经典型组患儿血清γ-谷氨酰转移酶(gamma-glutamyltransferase,γ-GT)显著偏高[158.00(122.80,309.30)vs.11.00(10.50,14.00)U/L,P=0.004],球蛋白[(15.55±3.45)vs.(24.26±4.37)g/L,P=0.018]和乳酸[1.05(0.98,1.68)vs.2.10(1.75,2.70)mmol/L,P=0.030]显著偏低,而丙氨酸转氨酶、天冬氨酸转氨酶和总胆汁酸组间差异无统计学意义(P>0.05)。血浆氨基酸谱分析发现经典型患儿血浆亮氨酸浓度显著高于中间型/硫胺素有效型患儿[3748.20(3135.00,4936.00)vs.620.40(531.20,1150.00)μmol/L,P=0.004]。γ-GT水平与亮氨酸(rs=0.826,P=0.003)水平、亮氨酸水平与异亮氨酸水平(rs=0.827,P=0.003)以及异亮氨酸水平与缬氨酸水平(rs=0.636,P=0.040)呈正相关关系。基因测序结果显示11例患儿分别携带有BCKDHA(n=4)和BCKDHB(n=7)基因变异,6例BCKDHB基因变异患儿为经典型MSUD。结论MSUD患儿的疾病发展及预后与γ-GT、支链氨基酸和基因型密切相关。Objective To summarize and analyze the clinical data of maple syrup urine disease(MSUD)patients to explore the correlation among clinical phenotype,biochemical markers and genotype.Methods The clinical data of 11 children with MSUD who were admitted to Guangzhou Women and Children’s Medical Center of Guangzhou Medical University between January 2011 and October 2016 were retrospectively collected.According to the clinical symptoms and prognosis,they were divided into classic type group(n=6)and intermediate/thiamine-effective group(n=5).The differences in biochemical metabolic markers between the two groups were compared,and the correlation between genotype and phenotype was analyzed.Results Compared to the intermediate/thiamine-effective group,the blood gamma-glutamyltransferase(γ-GT)level in the classic type group was significantly higher[158.00(122.80,309.30)vs.11.00(10.50,14.00)U/L,P=0.004],and the globulin[(15.55±3.45)vs.(24.26±4.37)g/L,P=0.018]and lactate[1.05(0.98,1.68)vs.2.10(1.75,2.70)mmol/L,P=0.030]levels in the classic type group were significantly lower,while the levels of alanine aminotransferase,aspartate aminotransferase and total bile acid were not different between the two groups(P>0.05).The plasma concentrations of leucine in the classic type group were higher than that in the intermediate/thiamine-effective group[3748.20(3135.00,4936.00)vs.620.40(531.20,1150.00)μmol/L,P=0.004].Theγ-GT level was positively correlated with the leucine level(rs=0.826,P=0.003),the leucine level was positively correlated with the iso-leucine level(rs=0.827,P=0.003),and the iso-leucine level was positively correlated with the valine level(rs=0.636,P=0.040).The results of gene sequencing showed that the 11 patients carried BCKDHA(n=4)and BCKDHB(n=7)gene mutations,respectively.Of these,6 patients with BCKDHB gene mutations were classic type.Conclusion The prognosis of MSUD is closely correlated to bloodγ-GT and branched-chain amino acids levels,as well as with genotype.

关 键 词：枫糖尿症 Γ-谷氨酰转移酶 支链氨基酸 BCKDHB基因 

分 类 号：R725.8[医药卫生—儿科]