{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T16:59:57Z","timestamp":1770224397604,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>A 7-month-old, spayed female, domestic longhair cat with L-2-hydroxyglutaric aciduria (L-2-HGA) was investigated. The aim of this study was to investigate the clinical signs, metabolic changes and underlying genetic defect. The owner of the cat reported a 4-month history of multiple paroxysmal seizure-like episodes, characterized by running around the house, often in circles, with abnormal behavior, bumping into obstacles, salivating and often urinating. The episodes were followed by a period of disorientation and inappetence. Neurological examination revealed an absent bilateral menace response. Routine blood work revealed mild microcytic anemia but biochemistry, ammonia, lactate and pre- and post-prandial bile acids were unremarkable. MRI of the brain identified multifocal, bilaterally symmetrical and T2-weighted hyperintensities within the prosencephalon, mesencephalon and metencephalon, primarily affecting the grey matter. Urinary organic acids identified highly increased levels of L-2-hydroxyglutaric acid. The cat was treated with the anticonvulsants levetiracetam and phenobarbitone and has been seizure-free for 16 months. We sequenced the genome of the affected cat and compared the data to 48 control genomes. L2HGDH, coding for L-2-hydroxyglutarate dehydrogenase, was investigated as the top functional candidate gene. This search revealed a single private protein-changing variant in the affected cat. The identified homozygous variant, XM_023255678.1:c.1301A&gt;G, is predicted to result in an amino acid change in the L2HGDH protein, XP_023111446.1:p.His434Arg. The available clinical and biochemical data together with current knowledge about L2HGDH variants and their functional impact in humans and dogs allow us to classify the p.His434Arg variant as a causative variant for the observed neurological signs in this cat.<\/jats:p>","DOI":"10.3390\/genes12050682","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["L2HGDH Missense Variant in a Cat with L-2-Hydroxyglutaric Aciduria"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-5929","authenticated-orcid":false,"given":"Matthias","family":"Christen","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-3311","authenticated-orcid":false,"given":"Nils","family":"Janzen","sequence":"additional","affiliation":[{"name":"Screening Labor Hannover, 30430 Hannover, Germany"},{"name":"Department of Clinical Chemistry, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Fraser","sequence":"additional","affiliation":[{"name":"Anderson Moores Veterinary Specialists, Winchester SO21 2LL, Hampshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian C.","family":"Sewell","sequence":"additional","affiliation":[{"name":"Biocontrol, 55128 Ingelheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8155-0041","authenticated-orcid":false,"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julien","family":"Guevar","sequence":"additional","affiliation":[{"name":"Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Sanchez-Masian","sequence":"additional","affiliation":[{"name":"Anderson Moores Veterinary Specialists, Winchester SO21 2LL, Hampshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/BF02312543","article-title":"L-2-Hydroxyglutaric aciduria: An inborn error of metabolism?","volume":"3","author":"Duran","year":"1980","journal-title":"J. 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