{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:58:35Z","timestamp":1760245115180,"version":"build-2065373602"},"reference-count":102,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Isovaleric acidemia (IVA, OMIM 243500) is an inherited disorder of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD), leading to an accumulation of isovaleric acid and its derivates 3-hydroxyisovaleric acid, isovaleryl (C5)-carnitine and isovalerylglycine in body fluids. The clinical presentation is highly variable, ranging from life-threatening metabolic crises with metabolic acidosis and hyperammonemia to a clinically asymptomatic only biochemical phenotype. Newborn screening for IVA has been established in many countries. Treatment consists of a protein-restricted diet combined with supplementation of carnitine and\/or glycine and emergency treatment in catabolic episodes. Still, evidence-based recommendations for the diagnosis and management of IVA patients with various phenotypes are lacking. Therefore, a systematic search and review of the literature was conducted to make suggestions for the care of patients with IVA based on both the available scientific evidence and consensus-derived expert conclusions. Based on a comprehensive set of literature data published between 1966 and 2024, 15 statements were phrased on the presentation, diagnosis, management, and outcome of IVA involving clinical, biochemical, and nutrition expertise. These statements can serve as a basis for more standardized care for IVA.<\/jats:p>","DOI":"10.3390\/ijns11040092","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:08Z","timestamp":1760114048000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Practical Considerations for the Diagnosis and Management of Isovaleryl-CoA-Dehydrogenase Deficiency (Isovaleric Acidemia): Systematic Search and Review and Expert Opinions"],"prefix":"10.3390","volume":"11","author":[{"given":"Eva","family":"Thimm","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children\u2019s Hospital, Faculty of Medicine, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anselma","family":"Riederer","sequence":"additional","affiliation":[{"name":"Institute for Medical Information Processing, Biometry, and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-6457","authenticated-orcid":false,"given":"Jerry","family":"Vockley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224-1334, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dries","family":"Dobbelaere","sequence":"additional","affiliation":[{"name":"Medical Reference Center for Inherited Metabolic Diseases, Jeanne de Flandre University Hospital and RADEME, Research Team for Rare Metabolic and Developmental Diseases, EA 59037 Lille, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monique","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Dokoupil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, University Hospital, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 80337 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6596-128X","authenticated-orcid":false,"given":"Ulrich A.","family":"Schatz","sequence":"additional","affiliation":[{"name":"Gynecological Tumour Genetics, TUM University Hospital, Technical University of Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-6850","authenticated-orcid":false,"given":"Regina","family":"Ensenauer","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children\u2019s Hospital, Faculty of Medicine, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Institute for Medical Information Processing, Biometry, and Epidemiology, Medical Faculty, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, 81377 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1073\/pnas.56.1.236","article-title":"Isovaleric acidemia: A new genetic defect of leucine metabolism","volume":"56","author":"Tanaka","year":"1966","journal-title":"Proc. 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