Abstract: Objective: To summarize initial clinical characteristics and gene mutations of infants with methylmalonic acidemia (MMA) and to analyze genotype-phenotype correlation. Methods: Infants diagnosed as MMA by genetic testing were recruited from June 2016 to June 2019 in Center for Molecular Medicine of Children's Hospital of Fudan University. Clinical characteristics and genetic test results were included for analysis. We compared patients' phenotypes based on genotype. Results: Forty-one infants were included in this study. Of them, twenty-six patients were males and the median age of onset was 21 days. Totally, 25 patients referred to hospital at neonatal time, 12 patients referred to hospital in 28 days to 6 months of age, and 4 patients referred to hospital in 6 months to 12 months of age. The most common chief complaints were poor postnatal response (24 patients) and suspected MMA by newborn screen (8 patients). Two genes (MUT and MMACHC) were detected in these patients and forty-seven kinds of pathogenic or likely pathogenic variants were detected. The hot mutations included c.729_730insTT, c.323G>A, and c.1677-1G>A for MUT gene. For MMACHC gene, c.609G>A, c.567dupT, and c.80A>G were hot mutations. A total of thirty-three patients presented clinical features, 22 patients detected with MUT gene variations and 11 patients detected with MMACHC gene variations. For two gene variations, the common clinical characteristics were dystonia, abnormal breathing, and feeding intolerance. No statistical differences were found in these two groups. Compared with patients with MMACHC mutations, patients with MUT mutations were more easily presented acidosis (50.0% vs 9.1%, P=0.027); however, patients with MMACHC mutations were easily presented cardiomyopathy than patients with MUT mutations (36.4% vs 4.5%, P=0.037). A total of five patients gave up treatments and died. Conclusion: Infants, who presented with poor response, dystonia, abnormal breathing, and feeding intolerance, should be consider the possibility of MMA.MMA patients with MMACHC variations were easily presented cardiomyopathy and patients with MUT variations were easily presented acidosis.