Systematic literature review on the methylmalonic acid level changes in transplanted patients with methylmalonic acidemia due to methylmalonyl-CoA mutase deficiency

Purpose Methylmalonic acidemia is caused by impaired metabolism of certain amino acids, odd-chain fatty acids and cholesterol side chains. One of the most severe forms of methylmalonic acidemia is caused by complete (mut0) or partial (mut-) deficiency of the methylmalonyl-coenzyme A mutase enzyme. The aim of this study was to examine the methylmalonic acid (MMA) levels in various body fluids (serum/plasma/blood or urine) of mutase deficient methylmalonic acidemia patients prior to and after liver (LT) or combined liver and kidney transplantation (LKT). Method Four databases were queried: Medline (via PubMed), Embase, Cochrane Database of Systematic Reviews, and PROSPERO from inception until February 3, 2025. Results A total of 26 articles including 176 patients with the mut subtype of methylmalonic acidemia, who underwent either LT or LKT were included. Both aggregated and individual-level data indicated a consistent and substantial reduction in MMA levels following LT and LKT. Differences between the paired plasma MMA samples of individual patients pre- and post-transplantation were significant in both LT ( n = 25; median of differences -74.5% relative to baseline; p -value < 0.0001) and LKT patients ( n = 14; median of differences = -88% relative to baseline; p -value < 0.001). Additionally, a significant decrease in urine MMA levels was observed post-transplant compared to pre-transplant in both LT ( n = 16; median of differences = -66.6% relative to baseline; p -value < 0.0001) and LKT ( n = 11; median of differences = -79.0% relative to baseline; p -value < 0.001). Conclusion Acknowledging that methylmalonic acidemia patients with transplants exhibit considerable intra- and interpatient variability in MMA levels, the substantial relative decrease observed after transplantation suggests that transplantation has a significant impact on MMA levels. Future research should investigate the correlation between decreasing MMA levels and improvements in metabolic stability and clinical outcomes after transplantation.