Inherited metabolic diseases are individually rare, but collectively common. Methylmalonic aciduria (MMA) is a typical inherited metabolic disease whereby patients frequently present in the first few days of life and, if left untreated, may progress to coma and death. Those patients who survive into later life often have long-term organ-specific complications, including kidney failure, severe neurological problems, and impaired vision. Although the monogenic causes of MMA are known, there is currently no cure. The development of causative treatments has been hindered in part by a lack of understanding of the dysfunction caused by disease at the cellular level and how this relates to disease progression in individual patients.