Mitochondrial Trifunctional Protein Deficiency: Severe Cardiomyopathy and Cardiac Transplantation

Area of Science:

• Biochemistry
• Genetics
• Pediatric Cardiology

Background:

• Mitochondrial trifunctional protein deficiency (MTPD) is a rare genetic disorder affecting fatty acid oxidation.
• Severe cardiomyopathy is a significant clinical manifestation of MTPD, often leading to poor outcomes in infancy.

Purpose of the Study:

• To report the first case of MTPD treated with cardiac transplantation.
• To evaluate the efficacy and outcome of cardiac transplantation in a pediatric MTPD patient.

Main Methods:

• Case report of two male siblings with MTPD.
• Newborn screening for fatty acid oxidation defects.
• Genome-wide exome sequencing to identify pathogenic mutations (HADHA).
• Description of clinical course, including dietary therapy, carnitine supplementation, and cardiac transplantation.

Main Results:

• One sibling presented with severe cardiomyopathy and died in infancy.
• The second sibling, diagnosed via newborn screening, received early dietary therapy and carnitine supplementation.
• Despite treatment, the second sibling required cardiac transplantation at age 3 due to rapid cardiac decline.
• The post-transplantation outcome was excellent, with no extra-cardiac MTPD manifestations by age 7.

Conclusions:

• Cardiac transplantation can be a successful therapeutic option for severe cardiomyopathy in MTPD.
• Early diagnosis through newborn screening and timely intervention are crucial.
• Further research is warranted to explore the long-term benefits of cardiac transplantation in MTPD.