[Analysis of 12 cases with methylmalonicacidemia cblA type]

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Methylmalonic acidemias (MMA) are inherited metabolic disorders affecting the vitamin B12-dependent pathway.
• CblA-type MMA is a specific subtype characterized by mutations in the MMAA gene.

Purpose of the Study:

• To investigate the clinical features, genetic variations, and outcomes of patients diagnosed with cblA-type methylmalonic acidemia.
• To identify common and novel MMAA gene variants associated with cblA-type MMA.

Main Methods:

• Analysis of clinical data, treatment regimens, and prognosis in 12 cblA-type MMA patients.
• Genetic analysis of the MMAA gene in affected individuals and their parents.

Main Results:

• Common symptoms include vomiting, dyspnea, and drowsiness. Eleven patients showed responsiveness to vitamin B12 therapy.
• Biochemical markers (propionylcarnitine, methylmalonic acid) significantly decreased post-treatment (P<0.05).
• Eight patients (66.7%) achieved normal development; 33.3% had residual neurodevelopmental deficits. Fourteen MMAA variants were identified, with c.365T>C being prevalent (29.2%), and six novel variants discovered.

Conclusions:

• Vomiting, dyspnea, and drowsiness are key clinical signs of cblA-type MMA.
• Vitamin B12 treatment is effective for the majority of patients.
• The MMAA variant c.365T>C may represent a hot spot in the Chinese population.