Long Term Follow-Up After Transplantation in Propionic Acidemia: A Retrospective French Pediatric and Adult Cohort...

Propionic acidemia (PA) is a rare inherited metabolic disorder associated with recurrent metabolic decompensations and chronic multisystemic complications. Liver transplantation (LT) may improve metabolic stability, but its long-term impact on organ involvement remains debated. We retrospectively studied 20 patients with PA transplanted between 1993 and 2024 in three French reference centers. Clinical, biochemical, and organ-specific data were collected before and after transplantation. Eighteen isolated LT and two combined liver-kidney transplantations were performed. Median age at transplantation was 13.6 years; median follow-up was 4.5 years. Indications included frequent metabolic decompensation (70%) and cardiomyopathy (35%). Four patients died perioperatively, three from cardiac causes; crude survival was 75%. Transplantation markedly improved metabolic stability and allowed significant dietary liberalization, with reduced need for enteral feeding. Cardiac involvement, present in 15 patients pre-transplant, showed variable evolution: 10 improved initially, but three deteriorated later, and one required heart transplantation. New neurological manifestations occurred in eight patients, with acute episodes including CNI-related encephalopathy. Psychiatric disorders progressed from 40% to 59% of patients, requiring treatment in seven. Renal impairment worsened post-LT to 70%, with mean measured glomerular filtration rate declining from 72 to 60 mL/min/1.73 m². LT improves metabolic and nutritional outcomes but does not consistently prevent chronic organ complications. In conclusion, early LT, before the onset of cardiac, neurologic, and psychiatric manifestations, should be considered on a case-by-case basis, as we could not demonstrate correlation between age at transplantation and organ involvement.