{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:00:36Z","timestamp":1769598036954,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T00:00:00Z","timestamp":1644278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Hyperammonaemic encephalopathy in adults is a rare condition in the absence of liver disease and is associated with a high mortality and risk of permanent neurological deficits. Seldomly, the condition is caused by an inborn error of metabolism in the urea cycle, triggered by an exogenic factor such as gastrointestinal haemorrhage, gastric bypass surgery, starvation, seizures, vigorous exercise, burn injuries, or drugs hampering the elimination of ammonia. Here, we present a fatal case of an unrecognized genetic ornithine transcarbamylase deficiency (OTCD) presenting with a subacute progressive encephalopathy. We review the current literature and discuss the differential diagnosis and treatment options. As swift diagnosis and initiation of treatment is vital, awareness of hyperammonaemic encephalopathy and its possible causes can help improve the prognosis of this condition.<\/jats:p>","DOI":"10.3390\/brainsci12020231","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T01:03:40Z","timestamp":1644368620000},"page":"231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hyperammonaemic Encephalopathy Caused by Adult-Onset Ornithine Transcarbamylase Deficiency"],"prefix":"10.3390","volume":"12","author":[{"given":"Bjarke Hammer","family":"Niclasen","sequence":"first","affiliation":[{"name":"Department of Neurology, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Therese","family":"Schelde-Olesen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads","family":"Astvad","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6905-4141","authenticated-orcid":false,"given":"Anders","family":"L\u00f8kke","sequence":"additional","affiliation":[{"name":"Department of Medicine, Little Belt Hospital, 7100 Vejle, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-6948","authenticated-orcid":false,"given":"Thomas","family":"Kr\u00f8ig\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7319-1368","authenticated-orcid":false,"given":"Helle H.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital, J.B. Winsloewsvej 4, 5000 Odense, Denmark"},{"name":"Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej 21, 5000 Odense, Denmark"},{"name":"BRIDGE-Brain Research\u2014Inter-Disciplinary Guided Excellence, Department of Clinical Research, J.B. Winsloewsvej 19, 5000 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,8]]},"reference":[{"key":"ref_1","unstructured":"Schaffalitzky De Muckadell, O.B., Hauns\u00f8, S., and Vilstrup, S. (2013). Medicinsk Kompendium, 18, Nyt Nordisk Forlag Arnold Busck."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1258\/acb.2011.011206","article-title":"Severe hyperammonaemia in adults not explained by liver disease","volume":"49","author":"Walker","year":"2012","journal-title":"Ann. Clin. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e897","DOI":"10.1097\/CCM.0000000000003278","article-title":"Features of Adult Hyperammonemia Not Due to Liver Failure in the I.C.U.","volume":"46","author":"Sakusic","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/bs.acc.2014.09.002","article-title":"Ammonia metabolism and hyperammonemic disorders","volume":"67","author":"Walker","year":"2014","journal-title":"Adv. Clin. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1002\/jimd.12292","article-title":"A retrospective study of adult patients with noncirrhotic hyperammonemia","volume":"43","author":"Stergachis","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.jhep.2010.11.031","article-title":"New insights on the mechanisms of valproate-induced hyperammonemia: Inhibition of hepatic N-acetylglutamate synthase activity by valproyl-CoA","volume":"55","author":"Aires","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1600-0404.1984.tb07799.x","article-title":"Hyperammonemia in asterixis induced by carbamazepine: Two case reports","volume":"69","author":"Ambrosetto","year":"1984","journal-title":"Acta Neurol. Scand."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.yebeh.2011.05.006","article-title":"Hyperammonemic encephalopathy related to valproate, phenobarbital, and topiramate synergism","volume":"21","year":"2011","journal-title":"Epilepsy Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1055\/s-0029-1245632","article-title":"[Antiepileptic drug-induced encephalopathy]","volume":"78","author":"Hansen","year":"2010","journal-title":"Fortschr. Neurol. Psychiatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1054\/jocn.2001.1011","article-title":"Primidone-induced hyperammonemic encephalopathy in a patient with cerebral astrocytoma","volume":"9","author":"Katano","year":"2002","journal-title":"J. Clin. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0278-5846(03)00166-0","article-title":"Asterixis and toxic encephalopathy induced by gabapentin","volume":"28","author":"Sechi","year":"2004","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"17","DOI":"10.2174\/157488609787354378","article-title":"Reyes\u2019s syndrome, encephalopathy, hyperammonemia and acetyl salicylic acid ingestion in a city hospital of Buenos Aires, Argentina","volume":"4","author":"Lemberg","year":"2009","journal-title":"Curr. Drug Saf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1136\/jnnp.2006.105353","article-title":"Aggravation of ataxia due to acetazolamide induced hyperammonaemia in episodic ataxia","volume":"78","author":"Kim","year":"2007","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1080\/10428190701509822","article-title":"Hyperammonemia encephalopathy: An important cause of neurological deterioration following chemotherapy","volume":"48","author":"Nott","year":"2007","journal-title":"Leuk. Lymphoma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.psym.2015.12.011","article-title":"Methamphetamine Intoxication Encephalopathy Associated with Hyperammonemia","volume":"57","author":"Lama","year":"2016","journal-title":"Psychosomatics"},{"key":"ref_16","first-page":"222","article-title":"Late-onset ornithine transcarbamylase deficiency: A potentially fatal yet treatable cause of coma","volume":"11","author":"Crosbie","year":"2009","journal-title":"Crit. Care Resusc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1111\/j.1463-1326.2009.01054.x","article-title":"Ammonia toxicity and its prevention in inherited defects of the urea cycle","volume":"11","author":"Walker","year":"2009","journal-title":"Diabetes Obes. Metab."},{"key":"ref_18","first-page":"865","article-title":"[Type II citrullinemia triggered by acetaminophen]","volume":"45","author":"Shiohama","year":"1993","journal-title":"No Shinkei"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.pcl.2017.11.004","article-title":"Inborn Errors of Metabolism with Hyperammonemia: Urea Cycle Defects and Related Disorders","volume":"65","author":"Summar","year":"2018","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_20","unstructured":"Ropper, A.H., Samuels, M.A., Klein, J.P., and Prasad, S. (2019). Adams & Victor\u2019s Principles of Neurology, McGraw-Hill Education. [11th ed.]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s11940-003-0037-5","article-title":"Urea Cycle Disorders","volume":"5","author":"Kleppe","year":"2003","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S1089-3261(05)70143-4","article-title":"Urea cycle disorders","volume":"4","author":"Burton","year":"2000","journal-title":"Clin. Liver Dis."},{"key":"ref_23","unstructured":"Lichter-Konecki, U., Caldovic, L., Morizono, H., Simpson, K., Mew, N.A., MacLeod, E., Adam, M.P., Ardinger, H.H., Pagon, R.A., and Wallace, S.E. (1993\u20132021). Ornithine Transcarbamylase Deficiency. Gene Reviews\u00ae, University of Seattle."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13613-020-00797-y","article-title":"Management of late onset urea cycle disorders-a remaining challenge for the intensivist?","volume":"11","author":"Redant","year":"2021","journal-title":"Ann. Intensive Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.1380040109","article-title":"Seven new mutations in the human ornithine transcarbamylase gene","volume":"4","author":"Tuchman","year":"1994","journal-title":"Hum. Mutat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/s12072-008-9078-x","article-title":"Acute fatal presentation of ornithine transcarbamylase deficiency in a previously healthy male","volume":"2","author":"Klein","year":"2008","journal-title":"Hepatol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1136\/pgmj.2010.235721rep","article-title":"Creutzfeldt-Jacob disease mimics, or how to sort out the subacute encephalopathy patient","volume":"87","author":"Murray","year":"2011","journal-title":"Postgrad. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"73","DOI":"10.9740\/mhc.2018.03.073","article-title":"Valproic acid-induced hyperammonemia: Incidence, clinical significance, and treatment management","volume":"8","author":"Baddour","year":"2018","journal-title":"Ment. Health Clin."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.2146\/ajhp080454","article-title":"Carbamazepine-induced hyperammonemia","volume":"66","author":"Adams","year":"2009","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/j.1651-2227.2008.00952.x","article-title":"Diagnosis, symptoms, frequency and mortality of 260 patients with urea cycle disorders from a 21-year, multicentre study of acute hyperammonaemic episodes","volume":"97","author":"Summar","year":"2008","journal-title":"Acta Paediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1002\/jimd.12096","article-title":"Challenges in diagnosing and managing adult patients with urea cycle disorders","volume":"42","author":"Stepien","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1373\/clinchem.2006.072033","article-title":"Equimolar ammonia interference in potassium measurement on the Osmetech OPTI CCA: A reply","volume":"52","author":"Lin","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_33","first-page":"V11200825","article-title":"[Hyperammonaemic encephalopathy in adults without liver diseases]","volume":"183","author":"Eriksen","year":"2021","journal-title":"Ugeskr Laeger."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/jimd.12100","article-title":"Suggested guideline for diagnosis and management of urea cycle disorders: First revision","volume":"42","author":"Burlina","year":"2019","journal-title":"J. Inherit. Metab. Dis."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/2\/231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:15:57Z","timestamp":1760134557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/2\/231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,8]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["brainsci12020231"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12020231","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,8]]}}}