Cardiac Manifestation in Propionic Acidemia: A 30-Year Single-Center Experience

Objectives: Propionic acidemia (PA) is an inborn error of metabolism caused by a deficiency of propionyl-CoA carboxylase. Apart from metabolic crises, PA typically presents with chronic organ dysfunction, including cardiac pathologies. Cardiomyopathy (CMP) and QTc prolongation are known to be life-threating complications in PA, but systematic analyses of cardiac phenotypes in PA patients are lacking.

Methods: We enrolled 18 patients diagnosed with PA in a retrospective single center study. Echocardiography data (left ventricular end-diastolic-diameter, LVEDD, including z-scores, systolic LV function - fractional shortening, mitral valve Doppler inflow patterns - E/A ratio) and 12-lead-electrocardiogram recordings (focus on corrected QT intervals, QTc, according to Bazett’s formula, repolarization disturbances and ventricular dysrhythmias) were analyzed. Symptomatic patients were dichotomized to the group “neonatal onset” (symptoms within 28 days of life) and “late onset” (symptoms after 28 days). Besides descriptive analysis, correlations between cardiac dysfunction, LVEDD and clinical parameters (age at onset, β-blocker therapy) were calculated.

Results: 18 patients with PA were enrolled, 17 of them were symptomatic (n = 1 asymptomatic) with a median age at diagnosis of 6.0 days. 15/17 (88%) were early onset and 2/17 (12%) late onset. CMP was diagnosed in 7/18 (39%) patients at a median age of 14.4 years; all of those were early onset patients. Mean QTc of all cases was 445 milliseconds (+/− 18.11 SD); however individual range was up to 564 milliseconds. QTc is not significantly correlated to age at onset or patient age but longer QTc is associated with higher LVEDD z-scores. Beta-blocker therapy leads to decreased QTc in all patients treated (n = 4). However, decreased QTc intervals were observed also in untreated patients. 11/18 (61%) individuals show pathological mitral valve inflow patterns (E/A ratio) demonstrating LV diastolic dysfunction.

Conclusion: CMP is a frequent complication of PA patients with early onset disease and is often associated with diastolic LV dysfunction. Mean QTc interval is prolonged and directly correlated to higher LVEDD z-scores. Beta-blocker therapy may be considered effective for prolonged QTc in PA. Prospective studies are warranted to further investigate predictors of LV dysfunction and QTc prolongation, aiming at early and effective therapy of cardiac complications in PA.

Die Autoren geben an, dass kein Interessenkonflikt besteht.