The re‐occurrence of cardiomyopathy in propionic acidemia after liver transplantation

Abstract

Cardiomyopathy is a frequent complication of propionic acidemia (PA). It is often fatal, and its occurrence is largely independent of classic metabolic treatment modalities. Liver transplantation (LT) is a treatment option for severe PA as the liver plays a vital role in metabolism of the precursors that accumulate in patients with PA. LT in PA is now considered to be a long‐lasting and valid treatment to prevent cardiac disease. The subject of this report had severe cardiomyopathy that largely disappeared prior to undergoing a LT. Three years following the transplant, there was recurrence of cardiomyopathy following a surgery that was complicated with a postoperative aspiration pneumonia. On his last hospital admission, he was presented with pulmonary edema and heart failure. He continued with episodes of intractable hypotension, despite maximum inotropic and diuretic support. He died following redirection of care. We conclude that lethal cardiomyopathy may develop several years after successful LT in patients with PA.

Natural history of propionic acidemia in the Amish population

“…In addition, successful liver transplant appears to achieve metabolic stabilization, resulting in fewer hospitalizations, less dietary restriction, and improved linear growth [ 28 , 29 ]. There have, however, been reports of new or recurrent cardiomyopathy following liver transplantation for PA [ 30 , 31 ], though it is unclear if cardiomyopathy is secondary to the presence of a second genetic condition in these individuals or if it is a result of immunosuppressant medications. This is especially important to keep in mind in the Amish since other genetic causes of cardiomyopathy and arrythmia are well described in them [ 32 ].…”

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

“…Nevertheless, re-occurrence of cardiomyopathy after LTX has been reported. 30 Although genotype-phenotype correlations in PA and MMA are unpredictable, determination of the genetic subtype in MMA can be helpful in weighing the risks versus benefits of transplantation especially in young patients detected by NBS: for example, patients with MMA due to Mut À and MMAA mutations are at lower risk of morbidity and mortality compared to MUT 0 and MMAB patients. 9 Skin fibroblast enzyme analysis is of limited value as it does not reliably predict the outcome, and is rarely carried out these days for confirmation of the diagnosis.…”

Cardiac Complications of Propionic and Other Inherited Organic Acidemias

“…Although PA treatment is not a focus of this Review , liver transplantation (LT) requires mentioning as it provides insights into the potential mechanisms of PA-induced cardiac dysfunction. For a more complete review of LT for the treatment of cardiac disease in PA, we refer readers to a recent study by Berry et al ( 111 ). In brief, liver transplantation (LT) has been proposed to be an effective way to treat PA by Leonard ( 112 ).…”

“…Indeed, LT has been shown to be effective in improving clinical outcome in PA and to largely eliminate keto-lactic-acidosis crises ( 114 , 115 ). Intriguingly, there have been several studies to suggest that LT can resolve cardiomyopathy in PA, beginning with the seminal report by Romano et al ( 105 ), and indeed, LT is now considered a valid treatment for cardiac disease in PA. More recently, however, Berry et al ( 111 ) reported a child whose cardiomyopathy had recurred following LT. This child was diagnosed with PA at 5 months and presented with signs of CHF at 9 years of age; subsequent echocardiogram found DCM with reduced LV EF (20%), and prolonged QTc (480 ms).…”

“…It appears to be unrelated to metabolic crises, since LT successfully reduces these episodes and improves overall outcomes. It should be noted, however, that propionate metabolites can remain elevated post-transplantation ( 111 , 116 ). This leads to the credence that these “propionate metabolites” may be the key drivers of cardiac pathogenesis (insights into the mechanisms underlying cardiac dysfunction in PA from experimental animal models).…”