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

Liver Transpl. 2018 Sep;24(9):1260-1270. doi: 10.1002/lt.25304.

Abstract

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 × 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.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Amino Acid Metabolism, Inborn Errors / surgery*
  • Biomarkers / blood
  • Databases, Factual
  • Energy Metabolism
  • Enteral Nutrition
  • Female
  • Gastrostomy
  • Graft Survival
  • Humans
  • Infant, Newborn
  • Kidney Transplantation
  • Liver Transplantation* / adverse effects
  • Male
  • Nutritional Status
  • Perioperative Care / adverse effects
  • Perioperative Care / methods*
  • Postoperative Complications / therapy
  • Propionic Acidemia / blood
  • Propionic Acidemia / diagnosis
  • Propionic Acidemia / surgery*
  • Recovery of Function
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers

Supplementary concepts

  • Methylmalonic acidemia