Liver Transplantation for Propionic Acidemia and Methylmalonic Acidemia: Perioperative Management and Clinical Outcomes

Propionic acidemia (PA) and methylmalonic acidemia (MMA) comprise the most common organic acidemias and account for profound morbidity in affected individuals. Although liver transplantation (LT) has emerged as a bulk enzyme-replacement strategy to stabilize metabolically fragile patients, it is not a metabolic cure because patients remain at risk for disease-related complications. We retrospectively studied LT and/or liver-kidney transplant in 9 patients with PA or MMA with additional focus on the optimization of metabolic control and management in the perioperative period. Metabolic crises were common before transplant. By implementing a strategy of carbohydrate minimization with gradual but early lipid and protein introduction, lactate levels significantly improved over the perioperative period (P < 0.001). Posttransplant metabolic improvement is demonstrated by improvements in serum glycine levels (for PA; P < 0.001 x 10(-14)), methylmalonic acid levels (for MMA; P < 0.001), and ammonia levels (for PA and MMA; P < 0.001). Dietary restriction remained after transplant. However, no further metabolic crises have occurred. Other disease-specific comorbidities such as renal dysfunction and cardiomyopathy stabilized and improved. In conclusion, transplant can provide a strategy for altering the natural history of PA and MMA providing stability to a rare but metabolically brittle population. Nutritional management is critical to optimize patient outcomes.