OBJECTIVES: Methylmalonic acidemia (MMA) is caused by deficiencies of specific enzymes in the breakdown pathways of amino acids and certain fats. Currently, liver or combined liver and kidney transplantation are the best available treatment options for severe cases. A systematic literature review (SLR) was conducted on the humanistic and economic burden of B12-unresponsive MMA, a more severe subtype of the disease, with special focus on pre- and post-transplant results.

METHODS: The SLR was conducted in compliance with the PRISMA 2020 guidelines. Articles were searched in the Medline, Embase, Scopus, Cochrane Review, PROSPERO and CRD databases, on 14 December 2022. Original studies presenting primary data about MMA mut0, mut-, cblB and MCEE subtypes or B-12 unresponsive MMA as a group were included. No geographical restriction and no publication date limit were applied. Backward and forward snowball search was conducted for additional results.

RESULTS: A total of 217 and 115 articles were identified by the searches, and 11 and 7 were included in the review for humanistic and economic burden, respectively. As a result of the snowball search, 5 more articles were added. Eight studies presented data on humanistic burden and 4 studies on economic burden in the context of transplantation. Studies showed slowing or improvement of cognitive decline after transplantation. No conclusive trend was found for physical impairment, but one study found decreased anxiety among caregivers. Studies on economic burden showed that the number of hospitalisations decreased significantly after transplantation, and average length-of-stay was reduced (78.8-90.6 days per year before and 7.4-28.2 days per year after transplantation).

CONCLUSIONS: Transplantation is found to decrease humanistic and economic burden in most studies, but the results clearly indicate that both areas are under-researched, and the heterogeneity of existing studies currently limit the possibility of a detailed description of the disease burden.