PPA2 deficiency—a rare cause of genetic cardiomyopathy: a case report

PPA2 deficiency is a rare mitochondrial disorder associated with non-ischemic cardiomyopathy, recurrent rhabdomyolysis, and sudden cardiac death (SCD). This case attempts to highlight the diagnostic and management challenges and contribute to the growing literature on mitochondrial disorders.

A 21-year-old female with lupus presented with chest pain that developed after hospitalisation for rhabdomyolysis during a viral illness. A cardiac MRI showed patchy late gadolinium enhancement suggestive of myocarditis. She was started on colchicine, but her symptoms persisted. Subsequent imaging revealed persistent myocardial inflammation without troponin elevation. She experienced further episodes of muscle aches and chest pain, prompting additional hospitalisations. Her sibling’s diagnosis of non-ischemic cardiomyopathy and need for cardiac transplantation raised suspicion for a genetic aetiology. Genetic testing confirmed compound heterozygosity for pathogenic PPA2 variants (c.380G > T and c.514G > A). She was managed with rhythm monitoring, alcohol avoidance, and genetic counseling.

PPA2 deficiency should be suspected in patients with unexplained cardiomyopathy, recurrent muscle involvement, and family history of SCD. Cardiac MRI findings of subepicardial and mid-myocardial fibrosis without troponin elevation are characteristic. Early identification allows for lifestyle modifications and consideration of preventive measures like an implantable cardioverter-defibrillator to mitigate the risk of SCD. This case highlights the importance of recognising PPA2 cardiomyopathy in young patients with recurrent cardiac and muscle symptoms. Comprehensive diagnostic evaluation, including genetic testing, is crucial for identifying this rare but life-threatening condition.