BACKGROUND

Methylmalonic acidemia (MMA) is a rare autosomal recessive disorder, that causes multisystem damage by accumulating toxic metabolites. These metabolites, particularly affecting nerve cells, contribute to suboptimal neurodevelopment in MMA patients. While fluctuations in these toxic metabolites are common in MMA patients, their precise impact on neurodevelopment remains unclear.

RESULTS

This study enrolled 20 MMA patients, comprising 14 vitamin B12 non-responsive (B12-NR) type and 6 vitamin B12 responsive (B12-R) type. Diverse parameters were assessed, including methylmalonic acid (MA), methylcitric acid (MCA), propionylcarnitine (C3), acetylcarnitine (C2), ammonia, glycine, and lactate. Cognitive function was evaluated using the Bayley-III and Wechsler intelligence scale, and brain imaging was conducted through magnetic resonance spectroscopy (MRS). The frequency and extent of fluctuations in toxic organic acids were computed based on blood test results. B12-NR type patients exhibited elevated levels of MA, MCA, C3, C3/C2 ratio and lactate, with more frequent and significant MA, MCA and C3 fluctuation than B12-R type patients. Brain imaging revealed central nervous system demyelination in B12-NR type patients, while B12-R type patients displayed normal MRS results. B12-R type patients exhibited significantly better neurocognitive outcomes, with higher scores in all domains.

CONCLUSION

Patients with B12-NR type MMA exhibit worse neurodevelopmental outcomes and more pronounced biochemical imbalances compared to those with B12-R type. Significant correlations were observed between higher fluctuation frequencies of toxic metabolites and lower developmental and IQ scores. These findings emphasize the importance of targeted strategies to manage organic acid fluctuations for improving neurodevelopmental outcomes in MMA.