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Published on: June 16, 2017
Clinical and genotypic analysis of 79 children with methylmalonic acidemia: a retrospective single-center study in
Huimin Yu1, Xiangbo Xie1,2, Chen Chen3
1Department of Pediatric Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Insights
Methylmalonic acidemia (MMA) presents heterogeneously in children, with combined MMA and isolated MMA showing distinct clinical, biochemical, and genetic features. Early diagnosis and treatment significantly improve outcomes for these hereditary metabolic disorders.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
- Metabolic Disorders
Background:
- Methylmalonic acidemia (MMA) is a prevalent hereditary metabolic disorder affecting infants and children.
- Understanding the diverse clinical presentations and genetic underpinnings of MMA is crucial for timely diagnosis and effective management.
- Previous studies have highlighted the variability in MMA, necessitating further investigation into subtype-specific characteristics.
Purpose of the Study:
- To investigate the age of onset, clinical phenotypes, genotypes, and biochemical features of 79 children diagnosed with MMA.
- To differentiate between combined MMA with hyperhomocysteinemia and isolated MMA based on clinical and molecular data.
- To provide data supporting early diagnosis and improved management strategies for MMA patients.
Main Methods:
- Retrospective analysis of 79 pediatric MMA patients diagnosed via genetic testing from January 2014 to December 2023.
- Data collection included age of onset, clinical manifestations, biochemical markers, neuroimaging findings, and genetic mutations.
- Comparison of clinical and genetic profiles between patients with combined MMA and isolated MMA.
Main Results:
- Seventy-nine children were analyzed: 47 with combined MMA and hyperhomocysteinemia, 32 with isolated MMA.
- Symptoms varied widely, with early onset linked to more severe outcomes; common symptoms included developmental delay, motor disorders, and intellectual disability.
- Distinct biochemical profiles and genetic mutations were identified for each subtype, with specific prevalent mutations noted (e.g., c.609G>A in combined MMA, mut c.729_730insTT in isolated MMA).
Conclusions:
- MMA exhibits significant heterogeneity, with distinct clinical, biochemical, and imaging differences between combined MMA and isolated MMA subtypes.
- Specific genetic mutations and biochemical abnormalities are associated with each MMA subtype, aiding in differential diagnosis.
- Early diagnosis and consistent treatment lead to substantial improvements in motor and intellectual deficits, underscoring the importance of timely intervention.
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.
