目的 探讨甲基丙二酸尿症合并同型半胱氨酸血症(简称合并型MMA)患儿存在心血管系统受累的临床特点及预后。方法 回顾性分析10 例合并型MMA 存在心血管系统受累患儿的临床资料,并对其转归进行随访。结果 10 例患儿中,4 例以气促、呼吸困难等心血管系统症状首发,3 例以水肿、血尿、蛋白尿等泌尿系统症状首发,3 例以发育落后、抽搐等神经系统症状首发。10 例患儿存在不同类型、不同严重程度的心血管系统损害。经过3 个月至8 年的治疗和随访,2 例先天性心脏病缺损自然闭合;1 例心律失常患儿无明显变化;5 例高血压患儿中,1 例失访,3 例血压已正常;5 例肺动脉高压患儿中,2 例死亡,2 例肺动脉压力恢复正常,1 例肺动脉压力仍轻度升高。7 例进行了MMACHC 基因检测,5 例存在c.80A>G突变。结论 对于以气促、呼吸困难起病的不明原因肺动脉高压和高血压患儿应注意代谢性疾病的可能。心血管系统受累的严重程度可能是影响合并型MMA 预后的重要原因。患儿心血管系统受累可能主要与MMACHC 基因c.80A>G 突变相关。
Abstract
Objective To study the clinical features and treatment outcomes of cardiovascular system involvement in children with methylmalonic aciduria combined with hyperhomocysteinemia (MMACHC).Methods The clinical data of 10 children with methylmalonic aciduria combined with hyperhomocysteinemia and who had cardiovascular system involvement were retrospectively analyzed and the treatment outcomes were followed up.Results In the 10 patients, there were 4 cases with initial presentations of cardiovascular system symptoms such as shortness of breath and dyspnea, 3 cases with urinary tract symptoms such as edema, hematuria and proteinuria, and 3 cases with nervous system symptoms such as developmental retardation and convulsions. The 10 patients had different types and severity of cardiovascular injuries. After 3 months to 8 years of follow-up, the congenital heart defects resolved naturally in 2 cases, and the patient with arrhythmia had no obvious changes. In 5 cases of hypertension, blood pressures recovered to normal in 3 cases, and 1 case was lost to follow-up. In 5 patients with pulmonary hypertension, 2 died, 2 recovered, and 1 case had mildly elevated pulmonary artery pressure. Seven patients underwent MMACHC gene testing, and 5 showed c.80A>G mutations.Conclusions Metabolic disease should be taken into account for the children with unexplained pulmonary hypertension and hypertension with the onset of the shortness of breath and dyspnea. The severity of cardiovascular system involvement might be one of the most important factors affecting the prognosis of children with MMACHC. Cardiavascular system involvement of the patients may be related to MMACHC c.80A>G mutations.
关键词
甲基丙二酸尿症 /
同型半胱氨酸血症 /
心血管系统 /
高血压 /
肺动脉高压 /
儿童
Key words
Methylmalonic aciduria /
Hyperhomocysteinemia /
Cardiovascular system /
Hypertension /
Pulmonary hypertension /
Child
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参考文献
[1] 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.
[2] 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.
[3] Carrillo-Carrasco N, Chandler RJ, Venditti CP. Combined methylmalonicacidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management[J]. J Inherit Metab Dis, 2012, 35(1):91-102.
[4] Profitlich LE, Kirmse B, Wasserstein MP, et al. High prevalence of structural heart disease in children with cblCtype methylmalonic aciduria and homocystinuria[J]. Mol Genet Metab, 2009, 98(4):344-348.
[5] Prada CE, Kirk EP, Hopp M, et al. Cardiac disease in methylmalonicacidemia[J]. J Pediatr, 2011, 159(5):862-864.
[6] GündüzM1, Ekici F, Ozaydın 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.
[7] Profitlich L, Kirmse B, Wasserstein MP, et al. Resolution of corpulmonale after medical management in a patient with cblC-type methylmalonic aciduria and homocystinuria:a case report[J]. Cases J, 2009, 2:8603.
[8] De Bie I, Nizard SD, Mitchell GA. Fetal dilated cardiomyopathy:an unsuspected presentation of methylmalonic aciduria and hyperhomocystinuria, cblC type[J]. Prenat Diagn, 2009, 29(3):266-270.
[9] Fu XW, Xu YK, Chan P, et al. Simple, fast, and simultaneous detection of plasma total homocysteine, methylmalonic acid, methionine, and 2-methylcitric acid using liquid chromatography and mass spectrometry (LC/MS/MS)[J]. JIMD Rep, 2013, 10:69-78.
[10] 宋金青, 杨艳玲, 孙芳, 等. 气相色谱-质谱联用分析在有 机酸尿症筛查与诊断中的应用[J]. 中国医刊, 2006, 41(2):38-40.
[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] 李建国, 黄建萍, 肖慧捷, 等. 甲基丙二酸尿症的肾脏损害 五例报告[J]. 中华儿科杂志, 2005, 43(11):810-813.
[13] Tu WJ, Chen H, He J. Methylmalonic aciduria:newborn screening in mainland China[J]. J Pediatr Endocrinol Metab, 2013, 26(3-4):399-400.
[14] Richard E, Desviat LR, Ugarte M, et al. Oxidative stress and apoptosis in homocystinuria patients with genetic remethylation defects[J]. J Cell Biochem, 2013, 114(1):183-191.
[15] Joseph J, Loscalzo J. Methoxistasis:integrating the roles of homocysteine and folic acid in cardiovascular pathobiology[J]. Nutrients, 2013, 5(8):3235-3256.
[16] 韩连书, 王斐, 胡宇, 等. 甲基丙二酸血症伴同型半胱氨酸 血症患儿临床及基因突变分析[J]. 中华内分泌代谢杂志, 2009, 25(4):405-408．
[17] 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.
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