Clinical and genotypic analysis of 79 children with methylmalonic acidemia: a retrospective single-center study in China.

OBJECTIVE

Methylmalonic acidemia (MMA) is a common hereditary disorder affecting infants and children. This study investigated the onset age, phenotypes, genotypes, and biochemical features of MMA in 79 children from a single center in Shandong Province, providing data to aid early diagnosis and management.

METHODS

The data were obtained from 79 children who were diagnosed with MMA through genetic analysis from January 2014 to December 2023. A retrospective analysis of the age of onset, clinical manifestations, biochemical characteristics, imaging features, gene mutations, and hospitalization status was performed.

RESULTS

Among the 79 patients, 47 had combined MMA with hyperhomocysteinemia, whereas 32 had isolated MMA. Symptoms occurred at any age, with some patients exhibiting symptoms within days after birth. Early-onset patients exhibited more severe symptoms and worse prognosis. The patients exhibited symptoms of delayed growth and development, motor disorders, intellectual disability, vomiting, and feeding difficulties. Most of the patients were prone to infection. A greater frequency of vomiting was reported among the isolated MMA patients. Echocardiography demonstrated that patients with comorbidities were more likely to develop cardiac abnormalities. MRI revealed more frequent abnormal white matter in the central nervous system in patients with combined MMA with hyperhomocysteinemia. Isolated MMA patients often demonstrated multiple brain abnormalities and severe symptoms. Blood biochemical analysis revealed that MMA patients exhibited various abnormal blood biochemical indicators, among which isolated MMA patients more often demonstrated hyperglycemia. Moreover, 89 mutation sites were detected in the combined MMA with hyperhomocysteinemia, with a total of 23 types being identified. Additionally, the c.609G>A mutation was the most prevalent. The isolated MMA demonstrated 64 gene mutation sites, with a total of 29 types being observed. Moreover, the mut c.729_730insTT was the most frequently detected mutation. With regular treatment, early diagnosed MMA patients demonstrated significant improvements in their motor and intellectual disabilities.

CONCLUSION

The symptoms in patients with MMA exhibited significant heterogeneity, with differences among subtypes in clinical characteristics, biochemical abnormalities, and imaging findings. The findings of this study contribute to a better understanding of the clinical features of MMA and provide valuable insights that may aid in improving patient outcomes.