cblC型甲基丙二酸血症合并同型半胱氨酸血症临床资料分析

摘要

Objective To analyze the clinical, biochemical and gene mutation features in patients with cblC methylmalonic acidemia combined with homocysteinemia (cb1C disease) and to improve knowledge of clinicians on clinical features of this disease in recent years.Methods Clinical data of 5 patients diagnosed with cblC disease from 2014 to 2016 was retrospectively analyzed.Clinical manifestations, laboratory examinations and gene mutation features were summarized and their clinical features and prognosis were summarized too.Results Clinical features were as following: onset of disease of all five patients was in infancy, who manifested various degree of feeding difficulty, development backwardness of mental, intelligence and sport ability, malnutrition.Levels of C3 (propionyl-carnitine), C3/C2 (ratio of propionyl-carnitine and acetylcamitine), C3/C0 (ratio of propionyl-carnitine and free carnitine), urine methylmalonic acid, lactic acid and serum homocysteine were increased.Increases of C3/C2 and C3/C0 were more significant than increase of C3.Blood ammonia increased slightly in 3 cases and head MRI scanning results of 4 patients were abnormal.Gene mutation features showed that 6 gene mutations were found, including c.104T>G (p.L35W), c.482G>A (p.R161Q), c.567_568insT (p.I190fs), 656_658del (p.219_220del) and 217C>T(p.R73X) with each mutation presented in one case, c.440_441del (p.G147fs) in 2 cases, c.609G>A(p.W203X) in 3 cases, and 609G>A was the most common mutation type found in this study.Clinical outcome was that all patients improved evidently after treatment of vitamin B12, folic acid, L-camitine, betaine, and vitamin B6.Conclusion The main clinical features of cblC disease include various degree of feeding difficulty, development backwardness of mental, intelligence and sport ability, malnutrition, significant increase of C3/C0, C3/C2, urine methylmalonic acid and homocysteine, and more significant increase of C3/C2 and C3/C0 than C3.Gene mutation of MMACHC is the cause of cblC disease.Knowledge on various clinical manifestations of cb1C disease in infancy and awareness of importance of neonatal blood tandem mass spectrometry allows early detection and interference of this disease and reduce disability rate of patients.%目的 分析cblC型甲基丙二酸血症合并同型半胱氨酸血症(cblC病)患者的临床、生化特点及基因突变特点,以提高临床医生对该病近年来的临床特点的认识.方法 回顾性分析2014至2016年5例cblC病患者的临床资料,总结临床表现、辅助化验检查和基因突变的特点,并对其临床特征及转归情况进行总结.结果 临床特点:5例患儿起病在婴儿期,均存在有不同程度的喂养困难、精神智力运动发育落后、营养不良;血C3(丙酰肉碱)、C3/C2(丙酰肉碱与乙酰肉碱比值)、C3/C0(丙酰肉碱与游离肉碱比值)、尿甲基丙二酸、乳酸及血同型半胱氨酸均增高,C3/C2和C3/C0比C3增高更显著,3例患儿血氨轻度增高,4例头颅MRI异常.基因突变特点:共发现6个基因突变,c.104T>G(p.L35W) 、c.482G>A(p.R161Q)、c.567_568insT(p.I190fs)、656_658del(p.219_220del)及217C>T(p.R73X)各1例;c.440-441del(p.G147fs)2例;c.609G>A(p.W203X)3例,609G>A是本研究中突变最多的类型.临床转归:给予VitB12、叶酸、左旋肉碱、甜菜碱及VitB6等治疗后病情明显好转.结论 cblC病的主要临床特征包括有不同程度的喂养困难、精神智力运动发育落后、营养不良;C3/C0、C3/C2、尿甲基丙二酸和同型半胱氨酸明显增高,C3/C2和C3/C0比C3增高更显著;MMACHC基因的突变是cblC病的原因;了解cblC病在婴儿期的各种临床表现和新生儿血串联质谱检测的重要性,可使此类疾病得到及时的诊断和干预,减少此类病人的致残率.