Pyrophosphatase 2 Deficiency: Clinical Presentation, Diagnosis and Management.
Nehoff H, Crozier I, Vernon H, James C, Fernández-Ávila AI, Bowes M, Gomez-Gonzalez E, Phoon C, DiLoreto K, Matsumura ME, van Haaften-Visser DY, Seaman C, Edwards MR, Morris-Rosendahl DJ, Simonetti K, Rippert AL, Ahrens-Nicklas RC, Tormey C, Bogush E, Kochhar A, Van Hove JLK, Kamsheh AM, Leone BA, Wortmann SB, Weintraub RG, Thompson WR, Silver ES, Zuckerman WA, Pearson J, Till J, Chatfield K, Goldstein A, McFarland R, Mayr JA, Doudney K
Circulation. Genomic and precision medicine, 2026 Oct
Abstract
PPA2 (pyrophosphatase 2) deficiency is a relatively newly recognized condition caused by biallelic variants in the gene. The gene encodes the mitochondrial enzyme PPA2, involved in the production of orthophosphate in the mitochondrial matrix. Affected individuals typically present with sudden cardiac death or acute heart failure following common viral illnesses in infants and toddlers, or following exposure to small amounts of alcohol as teenagers. The condition has a high mortality rate in these situations. Here, we explore the clinical presentations and current management of these patients with a view to guiding future emergency clinical management of cases.