Background: Isolated methylmalonic acidemia (MMA), an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type MMA). Because no universal consensus was made on whether mut-type MMA 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 MMA 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: Among patients diagnosed through NBS, 77 patients (45.8%) remained asymptomatic and 87 patients (53.4%) showed favorable neurocognitive outcomes. In contrast with individuals diagnosed clinically, only 30 cases (16.2%) developed healthily. In our comparison of patients whether detected by NBS, the age at diagnosis, the incidence of disease onset, the responsiveness of vitamin B12, age at the start of vitamin B12 treatment, levels of biochemical features before and after treatment, and the long-term prognosis were remarkably different ( P<0.01). The presence of disease onset and the blood C3/C2 ratio were more associated with poor outcomes of patients whether identified by NBS. Importantly, after considering NBS, the odd ratio of disease onset for poor outcome decreased and the unresponsiveness to vitamin B12 increased. Conclusion: Through preventing major disease-related events and allowing an earlier treatment initiation, NBS is beneficial for the prognosis of infants with mut-type MMA.
