Nonischemic Cardiomyopathy in Adult-Onset PPA2-Deficient Mitochondrial Disease

Nonischemic cardiomyopathy (NICM) can be caused by single-gene mutations, including genes such as inorganic pyrophosphatase 2 (PPA2) with multisystem effects.

A 28-year-old woman presenting with respiratory symptoms was discharged with a diagnosis of decompensated idiopathic NICM. Her NICM progressively worsened, and the patient underwent a heart transplant at the age of 38 and again at the age of 42. At age 47, genetic testing confirmed 2 mutations in the PPA2 gene that had caused her NICM.

This patient is to our knowledge the oldest published to date (48 years) presenting with cardiac symptoms who has PPA2 deficiency, a mitochondrial disease characterized by sudden cardiac death in infancy.

This case exemplifies the utility of employing genetic testing early in the diagnostic workup of NICM before applying the designation "idiopathic."