{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:45:06Z","timestamp":1760057106295,"version":"build-2065373602"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>PPA2 encodes the mitochondrial inorganic pyrophosphatase 2 enzyme, essential for energy metabolism. Biallelic loss-of-function variants have been associated with early-onset sudden cardiac death and cardiomyopathy, typically in infants or adolescents following minimal alcohol intake. Adult-onset presentations are extremely rare.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case summary<\/jats:title>\n                  <jats:p>We report a 58-year-old woman presenting with acute heart failure following a febrile viral infection. Echocardiography revealed severe left ventricular systolic dysfunction. Cardiac MRI showed diffuse myocardial fibrosis. Genetic testing identified a homozygous pathogenic variant in PPA2 (p.Arg127Leu). Family history included two brothers who died suddenly in adolescence, one after minimal alcohol intake. Our patient, after 6 months of follow-up with treatment for heart failure, had her systolic function normalized. However, an implantable cardioverter-defibrillator was placed due to extensive fibrosis and non-sustained ventricular tachycardia and the high risk of sudden death associated with the disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This is the first known case of PPA2-related cardiomyopathy presenting with reversible heart failure in adulthood, highlighting an expanded phenotypic spectrum. Recognizing adult-onset cases is crucial, as it provides an opportunity to manage these patients in a personalized manner and to prevent complications, decompensation, or fatal outcomes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjcr\/ytaf475","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T05:28:01Z","timestamp":1758691681000},"source":"Crossref","is-referenced-by-count":0,"title":["Acute heart failure in adulthood as the first manifestation of a homozygous pyrophosphatase 2 variant, expanding the phenotypic spectrum: a case report"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5020-4381","authenticated-orcid":false,"given":"Natalia","family":"Marrero Negr\u00edn","sequence":"first","affiliation":[{"name":"Departament of Cardiology, Complejo Hospitalario Universitario Insular-Materno Infantil , Av Maritima s\/n, Las Palmas de Gran Canaria 35016 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,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose David","family":"Uma\u00f1a Monz\u00f3n","sequence":"additional","affiliation":[{"name":"Departament of Cardiology, Complejo Hospitalario Universitario Insular-Materno Infantil , Av Maritima s\/n, Las Palmas de Gran Canaria 35016 ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"2025100910321176500_ytaf475-B1","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.ajhg.2016.06.027","article-title":"Sudden cardiac death due to deficiency of the mitochondrial inorganic pyrophosphatase PPA2","volume":"99","author":"Kennedy","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2025100910321176500_ytaf475-B2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.ajhg.2016.06.021","article-title":"Biallelic PPA2 mutations cause sudden unexpected cardiac arrest in 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