P016: Novel stem cell models of mitochondrial inorganic pyrophosphatase 2 (PPA2) deficiency reveal pathologies and targets for therapy

Inorganic pyrophosphatase 2 (PPA2) deficiency (MIM 617222) is a recently described, rare autosomal recessive mitochondrial disorder caused by pathogenic variants in the PPA2 gene. This disease presents in one of 2 ways: infantile sudden cardiac death in the setting of illness, or as an ethanol-induced sudden cardiac death, typically in adolescents, triggered by ingestion of minimal amounts of ethanol. Importantly, outside of acute episodes, patients are essentially asymptomatic with no activity limitations, and there is no established genotype-phenotype association, with both early- and late-onset presentations occurring within the same families.