Safety, efficacy, and timing of transplantation(s) in propionic and methylmalonic aciduria

J Inherit Metab Dis. 2023 May;46(3):466-481. doi: 10.1002/jimd.12613. Epub 2023 Apr 24.

Abstract

Propionic (PA) and methylmalonic aciduria (MMA) share many clinical similarities, which include the risk of acute metabolic encephalopathies, and some long-term complications, such as optic neuropathy, pancreatic involvement, developmental disability, and similar management approaches, but they also represent distinct clinical and biochemical entities. In the severe forms of PA and MMA, most long-term complications cannot be prevented with conventional clinical management. Organ transplantation represents a form of partial enzyme replacement to improve the long-term outlook for these disorders. There is evidence that early liver transplant in both disorders greatly improves metabolic stability and reduces the risk of long-term complications. For MMA, early liver transplant reduces methylmalonic acid levels which in turns reduces its effects on kidneys, and therefore slows progression of chronic kidney disease. However, established organ damage cannot be reversed. For patients with MMA who present with chronic kidney disease, consideration should be given for combined liver and kidney transplants. Transplantation in PA and MMA carries a high risk of complications and requires highly specialised pre-operative and peri-operative management. Involvement of a multidisciplinary team is essential and should include metabolic team, nephrologist, hepatologist, hepatobiliary and renal transplant surgeons, anaesthesiologists, cardiologists, intensive care team, dieticians and specialist nurses. These patients require life-long multidisciplinary follow-up. There is increasing evidence in the literature on excellent short to medium-term patient and allograft survival following transplantation when patients are managed by a multidisciplinary team in a specialist centre. Improved early diagnosis and reductions in transplant-related mortality and morbidity have allowed early transplantation to be used electively to further improve the outcome.

Keywords: liver and kidney transplantation; liver transplantation; methylmalonic aciduria; propionic aciduria.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors* / diagnosis
  • Humans
  • Kidney Transplantation* / adverse effects
  • Liver Transplantation*
  • Methylmalonic Acid
  • Propionic Acidemia* / diagnosis
  • Renal Insufficiency, Chronic* / complications

Substances

  • Methylmalonic Acid

Supplementary concepts

  • Methylmalonic acidemia