PDF(Pubmed)
Abstract：
BACKGROUND: Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course.
METHODS: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome.
RESULTS: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality.
CONCLUSIONS: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.
METHODS: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome.
RESULTS: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality.
CONCLUSIONS: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.
摘要：
背景：分离型甲基丙二酸血症，丙酸代谢的常染色体隐性遗传疾病，通常是由甲基丙二酰辅酶A变位酶基因（mut型）的突变引起的。由于在新生儿筛查（NBS）中是否应包括突变型甲基丙二酸血症没有达成普遍共识，我们的目的是比较NBS检测到的这种疾病与临床检测到的疾病的结局,并研究NBS对病程的影响.
方法：在本研究中，将NBS诊断的168例突变型甲基丙二酸血症患者与疾病发作后未进行NBS诊断的210例患者进行比较。回顾性分析中国7个代谢中心患者的临床资料,包括最初的表现，生化代谢物，维生素B12治疗的反应，和基因变异，探讨不同因素对长期结果的影响。
结果：通过临床诊断的患者的比较，NBS检测到的患者在诊断时年龄较小，发病率较低，更好的反应的维生素B12，年轻的年龄在开始治疗，治疗前后生化特征水平较低，远期预后较好(P<0.01)。疾病发作，无论NBS是否确定,血液C3/C2比值和维生素B12无反应与患者的不良结局呈正相关.此外，上述因素以及治疗开始时的年龄与死亡率呈正相关.
结论：这项研究高度证明NBS可以预防重大疾病相关事件，并允许更早开始治疗。作为关键的预后因素，NBS有利于改善患有mut型甲基丙二酸血症的婴儿的总体生存率。
方法：在本研究中，将NBS诊断的168例突变型甲基丙二酸血症患者与疾病发作后未进行NBS诊断的210例患者进行比较。回顾性分析中国7个代谢中心患者的临床资料,包括最初的表现，生化代谢物，维生素B12治疗的反应，和基因变异，探讨不同因素对长期结果的影响。
结果：通过临床诊断的患者的比较，NBS检测到的患者在诊断时年龄较小，发病率较低，更好的反应的维生素B12，年轻的年龄在开始治疗，治疗前后生化特征水平较低，远期预后较好(P<0.01)。疾病发作，无论NBS是否确定,血液C3/C2比值和维生素B12无反应与患者的不良结局呈正相关.此外，上述因素以及治疗开始时的年龄与死亡率呈正相关.
结论：这项研究高度证明NBS可以预防重大疾病相关事件，并允许更早开始治疗。作为关键的预后因素，NBS有利于改善患有mut型甲基丙二酸血症的婴儿的总体生存率。
