{{Infobox medical condition (new) | name = Argininemia | image = Arginin_-_Arginine.svg | alt = 2D chemical structure of arginine | caption = Arginine | symptoms = Lethargy, Dehydration<ref name=gen/><ref name=emed/> | synonyms='''Arginase deficiency'''<ref>{{OMIM|207800}}</ref> | onset = | duration = | types = | causes = Mutations in the ARG1 gene<ref name=arg/><ref name=ah/> | risks = | diagnosis = Urinary orotic acid concentration<ref name=gen/> | differential = | prevention = | treatment = Limited protein intake, sodium benzoate<ref name=emed/> | medication = | prognosis = | frequency = | deaths = }}
'''Argininemia''' is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high; the nervous system is especially sensitive to the effects of excess ammonia.<ref name="gen">{{Cite journal |last1=Wong |first1=Derek |last2=Cederbaum |first2=Stephen |last3=Crombez |first3=Eric A. |date=1 January 1993 |title=Arginase Deficiency |url=https://www.ncbi.nlm.nih.gov/books/NBK1159/ |journal=GeneReviews |pmid=20301338 |access-date=20 November 2016}}update 2014</ref><ref name="nih">{{Cite web |date= |title=Arginase deficiency |url=https://medlineplus.gov/genetics/condition/arginase-deficiency/ |access-date=20 November 2016 |website= |publisher=National Library of Medicine}} {{Source attribution}}</ref>
==Signs and symptoms== The presentation of argininemia, in those that are affected, is consistent with the following:<ref name=gen/><ref name="emed">{{Cite web |date=15 April 2016 |title=Arginase Deficiency: Background, Pathophysiology, Epidemiology |url=http://emedicine.medscape.com/article/941838-overview |access-date=28 November 2016 |website=eMedicine}}</ref> {{columns-list|colwidth=30em| * Lethargy * Dehydration * Hypotonia * Stunted growth * Microcephaly * Seizures }}
==Genetics==
[[Image:autorecessive.svg|thumb|right|Argininemia has an autosomal recessive pattern of inheritance.]]
Mutations in the ''ARG1'' gene cause argininemia, which belongs to a class of genetic diseases called urea cycle disorders.<ref name="arg">{{Cite web |title=ARG1 gene |url=https://medlineplus.gov/genetics/gene/arg1/ |access-date=28 November 2016 |website=Genetics Home Reference}}</ref><ref name="ah">{{Cite journal |last1=Ah Mew |first1=Nicholas |last2=Lanpher |first2=Brendan C. |last3=Gropman |first3=Andrea |last4=Chapman |first4=Kimberly A. |last5=Simpson |first5=Kara L. |last6=Summar |first6=Marshall L. |date=1 January 1993 |title=Urea Cycle Disorders Overview |url=https://www.ncbi.nlm.nih.gov/books/NBK1217/ |journal=GeneReviews |pmid=20301396 |access-date=20 November 2016}}update 2015</ref> The urea cycle is a sequence of reactions that occurs in liver cells (hepatocytes). This cycle processes excess nitrogen, generated when protein is used by the body, making urea that is excreted via the kidneys.<ref>{{Cite book |last1=Hames |first1=David |url=https://books.google.com/books?id=BFcUn93iac0C&q=urea+cycle+biochemistry&pg=PA408 |title=Instant Notes in Biochemistry. |last2=Hooper |first2=Nigel |date=2005 |journal=Annales de Biologie Clinique |publisher=Taylor & Francis Ltd. |isbn=9780203967621 |edition=3rd |volume=58 |location=Hoboken |page=408 |language=en |pmid=11098183 |access-date=28 November 2016 |issue=6}}</ref>
The ''ARG1'' gene provides instructions for making an enzyme called arginase, this enzyme controls the last steps of the urea cycle, which produces urea by extracting nitrogen from arginine.<ref name=arg/> In people with arginase deficiency, arginase is missing, and arginine is not broken down properly. consequently, urea cannot be produced and excess nitrogen accumulates in the blood in the form of ammonia.<ref name="nih" /> Ammonia and arginine are thought to cause neurological problems and other symptoms of arginase deficiency.<ref name=gen/>
This condition is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene are required to inherit the disorder.<ref name=nih/>
Both parents of an individual with an autosomal recessive disorder are carriers of one copy of the gene, but usually do not have the disorder.<ref name=nih/>
==Diagnosis== The diagnosis for argininemia can usually be done using fetal blood sample.<ref>{{Cite book |last1=Wyllie |first1=Robert |url=https://books.google.com/books?id=rlIiCgAAQBAJ&q=arginase+deficiency+diagnosis&pg=PA886 |title=Pediatric Gastrointestinal and Liver Disease |last2=Hyams |first2=Jeffrey S. |last3=Kay |first3=Marsha |date=2015 |publisher=Elsevier Health Sciences |isbn=9780323370219 |page=886 |language=en}}</ref> One can look for the following indicators as to the presence of the condition:<ref name=gen/> * Plasma ammonia concentration. * Urinary orotic acid concentration * Red blood cell arginase enzyme activity (measurement)
==Treatment== thumb|Glycerol phenylbutyrate The treatment for people with argininemia includes:<ref name=emed/> * Sodium benzoate * Sodium phenylbutyrate * Carglumic acid * Glycerol phenylbutyrate * Palonosetron * Ondansetron hydrochloride
Pegzilarginase (Loargys) was approved for medical use in the European Union in December 2023.<ref name="Loargys Product information">{{Cite web |date=18 December 2023 |title=Loargys Product information |url=https://ec.europa.eu/health/documents/community-register/html/h1774.htm |access-date=26 December 2023 |website=Union Register of medicinal products}}</ref>
==References== {{Reflist|32em}}
==Further reading== * {{Cite book |url=https://books.google.com/books?id=IVaGNJ3Htz8C&q=arginase+deficiency+symptoms&pg=PA300 |title=Inborn metabolic diseases diagnosis and treatment |date=2012 |publisher=Springer |isbn=9783642157202 |editor-last=Saudubray |editor-first=Jean-Marie |edition=5th |location=Berlin |language=en |access-date=28 November 2016 |editor-last2=van den Berghe |editor-first2=Georges |editor-last3=Walter |editor-first3=John H. |editor-last4=Berghe |editor-first4=Georges van den}} * {{Cite book |last=Piña-Garza |first=J. Eric |url=https://books.google.com/books?id=jkMPxMpshlEC&q=arginase+deficiency+symptoms&pg=PA6 |title=Fenichel's Clinical pediatric neurology a signs and symptoms approach |date=2013 |publisher=Saunders |isbn=978-1455748129 |edition=7th |location=Oxford |language=en |access-date=28 November 2016}}
== External links == {{Medical resources | DiseasesDB = 29677 | ICD10 = E72.2 | ICD9 = | ICDO = | OMIM = 207800 | MedlinePlus = | eMedicineSubj = ped | eMedicineTopic = 132 | MeshID = D020162 | GeneReviewsNBK = NBK1159 | GeneReviewsName = Arginase Deficiency | ICD10CM = {{ICD10CM|E72.21}} | Orphanet = 90 }} {{Scholia|topic}} {{Amino acid metabolic pathology}} {{Medicine}} {{Authority control}}
Category:Amino acid metabolism disorders Category:Autosomal recessive disorders Category:Disorders causing seizures