Cardiac Involvement in Classical Organic Acidurias: Clinical Profile and Outcome in a Pediatric Cohort

Area of Science:

• Metabolic disorders
• Cardiology
• Pediatric medicine

Background:

• Cardiac involvement is a serious complication in organic acidurias (OAs), often leading to disability and death.
• Dilated cardiomyopathy (DCM) is the most common cardiac phenotype in OA patients.
• The long-term effects of cardiac complications in OAs require further investigation.

Purpose of the Study:

• To investigate the natural history and impact of cardiac complications in patients with classical organic acidurias (OAs).
• To assess the prognostic significance of cardiac involvement in OA patients.
• To evaluate the role of liver transplantation in managing cardiac complications in OAs.

Main Methods:

• A retrospective study of 60 patients diagnosed with OAs (propionic acidemia, methylmalonic acidemia, isovaleric acidemia, maple syrup urine disease) between 2000 and 2022.
• Systematic assessment of cardiac status at baseline and during follow-up.
• Analysis of major adverse cardiac events (MACEs) and outcomes, including liver transplantation.

Main Results:

• Cardiac anomalies were present in 23/60 OA patients, exclusively in propionic acidemia (PA) and methylmalonic acidemia (MMA).
• Dilated cardiomyopathy (DCM) was observed in 17/23 patients, associated with the poorest prognosis.
• Major adverse cardiac events (MACEs) at 5 years were 55% in PA with cardiomyopathy and 35% in MMA with cardiomyopathy.
• Liver transplantation in seven patients (12%) with PA or MMA stabilized metabolic and cardiac function.

Conclusions:

• Approximately one-third of children with classical OAs experience cardiac involvement, primarily DCM in PA and MMA, often leading to poor outcomes (>50%).
• Cardiac complications significantly impact the prognosis of OA patients.
• Accurate etiological diagnosis of OAs is crucial for effective management and risk stratification.