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Heart and heart-liver transplantation in Amish patients with propionic acidemia
Evan H Whitehead1, Jeffrey Bennett2, Pavan Bhat1
1Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
Insights
Propionic acidemia (PA) in Amish patients can cause severe heart failure. Combined heart/liver transplantation may be a viable option for managing this rare metabolic disorder.
Area of Science:
- Genetics
- Metabolic Disorders
- Cardiology
Background:
- Propionic acidemia (PA) is a genetic disorder affecting propionyl-CoA carboxylase activity.
- PA leads to toxic metabolite accumulation from odd-chain fatty acids and branched-chain amino acids.
- A specific PA variant in the Amish population often presents as dilated cardiomyopathy.
Purpose of the Study:
- To describe the clinical course and management of Amish patients with PA-associated dilated cardiomyopathy.
- To evaluate treatment strategies, including heart transplantation, for end-stage heart failure in this population.
Main Methods:
- Case series reporting on three Amish patients with genetically confirmed PA and end-stage heart failure.
- Review of treatment outcomes, including heart transplantation and combined heart/liver transplantation.
Main Results:
- One patient had a successful heart transplant without complications.
- Another patient experienced recurrent cardiogenic shock post-transplant due to metabolic decompensation.
- A third patient was treated with combined heart/liver transplantation.
Conclusions:
- Managing PA-related metabolic cardiomyopathies presents unique challenges.
- A multidisciplinary approach is crucial for optimizing outcomes in these patients.
Background And Aim:
Propionic acidemia (PA) is a genetic metabolic disorder caused by deficient activity of the enzyme propionyl-CoA carboxylase, resulting in accumulation of toxic metabolites during catabolism of odd-chain fatty acids and branched-chain amino acids. Most PA occurs in compound heterozygotes, typically presenting with metabolic acidosis and seizures in infancy. A milder phenotype of PA is prevalent in the Amish population due to a founder missense variant in PCCB (c.1606 A > G; p.Asn536Asp) and is frequently present as an isolated dilated cardiomyopathy in adolescence.
Methods And Results:
Here we report our experience with three Amish patients with genetically confirmed PA and end-stage heart failure. While one patient underwent successful heart transplantation with no complications, another developed recurrent cardiogenic shock after transplant due to metabolic decompensation. Based on this experience, a subsequent patient was treated with combined heart/liver transplantation.
Conclusions:
These cases highlight unique challenges in managing patients with metabolic cardiomyopathies and emphasize the importance of a multidisciplinary approach to achieve the best possible outcomes.
