Long-term follow-up of Chinese patients with methylmalonic acidemia of the cblC and mut subtypes.

Abstract

Background: Methylmalonic acidemia (MMA) is the most common organic acidemia in China, with cblC (cblC-MMA) and mut (mut-MMA) being the predominant subtypes. The present study aimed to investigate the prognostic manifestations and their possible influence in patients with these two subtypes.

Methods: A national multicenter retrospective study of patients with cblC-MMA and mut-MMA between 2004 and 2022 was performed. We compared the clinical features between patients with two subtypes or diagnosed with or without newborn screening (NBS) and further explored the potentially influential factors on the prognosis.

Results: The 1617 enrolled MMA patients included 81.6% cblC-MMA patients and 18.4% mut-MMA patients, with an overall poor prognosis rate of 71.9%. These two subtypes of patients showed great differences in poor prognostic manifestations. The role of NBS in better outcomes was more pronounced in cblC-MMA patients. Predictors of outcomes are "pre-treatment onset", "NBS", variants of c.80A > G and c.482G > A and baseline levels of propionylcarnitine and homocysteine for cblC-MMA; "pre-treatment onset", "responsive to vitB12", variants of c.914T > C and baseline propionylcarnitine and propionylcarnitine/acetylcarnitine ratio for mut-MMA. Besides, prognostic biochemical indicators have diagnostic value for poor outcomes in mut-MMA.

Conclusions: The study provided potential predictors of the long-term outcome of patients with cblC-MMA and mut-MMA.

Impact: Predictors of outcomes are "pre-treatment onset", "NBS", MMACHC variants of c.80A > G and c.482G > A and baseline propionylcarnitine and homocysteine for cblC-MMA, "pre-treatment onset", "responsive to vitB12", MMUT variants of c.914T > C and baseline propionylcarnitine and propionylcarnitine/acetylcarnitine ratio for mut-MMA. This study with larger sample sizes effectively validated the prediction power and emphasized the importance of NBS in improving the outcomes of both MMA subtypes. The study enhances understanding of the phenotypic and prognostic variations of MMA disease and the predictors will help in the improvement of diagnosis and treatment strategies to achieve a better prognosis for MMA.