Alcohol-Induced Sudden Cardiac Death in a Teenager With PPA2 Gene Mutations

Abstract The PPA2 gene encodes a mitochondrial pyrophosphatase protein. Mutations in the gene are inherited in an autosomal recessive fashion and, when mutated, function to induce mitochondrial ATP production failure resulting in increased stress on the heart and sudden cardiac death, especially when combined with alcohol. Herein, we describe a case of a 19-year-old female patient with a history of “alcohol intolerance” who was found unexpectedly deceased after consuming a minimal amount of alcohol. Histological examination of her heart revealed widespread fibrosis of the left ventricle and the interventricular septum. Other findings include hypertrophied myocytes, including some with pleomorphic nuclei. Genetic studies were performed on postmortem blood, revealing heterozygous PPA2 gene mutations, the pathogenic variant c.683C>T (p.Pro228Leu), and the other variant c.814C>T (p.His272Tyr), a novel variant of undetermined significance. We propose that the variant of undetermined significance is likely a pathogenic mutation due to the decedent's phenotype.