{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:42:29Z","timestamp":1765888949416,"version":"3.41.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Isovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report the case of a Chinese patient with IVA who was admitted to Tianjin Children's Hospital and followed up for 8 years. Genetic analysis of the patient and his parents was conducted using the whole-exome sequencing and Sanger sequencing. We searched for similar reported cases in the PubMed and Wanfang databases using the term \u201cisovaleric acidaemia,\u201d reviewed the related literature to obtain a summary of the clinical and genetic characteristics, and analyzed the genotype\u2013phenotype correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the <jats:italic>IVD<\/jats:italic> gene, including the unreported variant c.224A&amp;gt;G (p.Asn75Ser) and the reported variant c.1195G&amp;gt;C (p.Asp399His). The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. Another 154 cases identified in 25 relevant references were combined with this case, resulting in a sample of 155 patients, including 52 asymptomatic patients, 64 with neonatal onset, and 39 with the chronic intermittent disease with onset from ages of 1 month to 10 years (median age, 2 years). Among articles that reported sex, the male-to-female ratio was 1:1.06. The cardinal symptoms included vomiting, lethargy, \u201csweaty foot\u201d odor, poor feeding, developmental delay, and epilepsy. The proportion of variants in regions 123\u2013159 and 356\u2013403 of the IVD protein was greater in symptomatic patients than in asymptomatic patients. Conversely, in asymptomatic patients, the proportion of variants in the 282\u2013318 region was greater than in symptomatic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case report describes an unreported variant c.224A&amp;gt;G (p.Asn75Ser) of the <jats:italic>IVD<\/jats:italic> gene, and summarizes previously reported cases. Furthermore, the correlation between the genotype and clinical phenotype of IVA is analyzed to improve the understanding of this disease.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2022.928334","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T06:21:48Z","timestamp":1658989308000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of the genotype\u2013phenotype correlation in isovaleric acidaemia: A case report of long-term follow-up of a chinese patient and literature review"],"prefix":"10.3389","volume":"13","author":[{"given":"Xingmiao","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinquan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxuan","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongbin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meifang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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 Natl Acad Sci U S A."},{"key":"B2","doi-asserted-by":"publisher","first-page":"8455","DOI":"10.1021\/bi970422u","article-title":"Structure of human isovaleryl-CoA dehydrogenase at 2. 6 A resolution: structural basis for substrate specificity","volume":"36","author":"Tiffany","year":"1997","journal-title":"Biochemistry."},{"key":"B3","doi-asserted-by":"publisher","first-page":"436","DOI":"10.12998\/wjcc.v9.i2.436","article-title":"Neonatal isovaleric acidemia in China: a case report and review of literature","volume":"9","author":"Wu","year":"2021","journal-title":"World J Clin Cases."},{"key":"B4","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/j.1442-200X.2011.03488.x","article-title":"Phenotypic and mutation spectrums of Thai patients with isovaleric acidemia","volume":"53","author":"Vatanavicharn","year":"2011","journal-title":"Pediatr Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/ajmg.c.30089","article-title":"Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity","author":"Vockley","year":"2006","journal-title":"Am j med genet C Semin med genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/0003-9861(87)90072-5","article-title":"Biosynthesis of four rat liver mitochondrial acyl-CoA dehydrogenases: in vitro synthesis, import into mitochondria, and processing of their precursors in a cell-free system and in cultured cells","volume":"252","author":"Ikeda","year":"1987","journal-title":"Arch Biochem Biophys."},{"key":"B7","doi-asserted-by":"publisher","first-page":"16321","DOI":"10.1016\/S0021-9258(18)71624-4","article-title":"Molecular cloning and nucleotide sequence of cDNAs encoding the precursors of rat long chain acyl-coenzyme A, short chain acyl-coenzyme A, and isovaleryl-coenzyme A dehydrogenases. 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