Editing Urea cycle (section)

==Urea cycle disorders==
Urea cycle disorders are rare and affect about one in 35,000 people in the [[United States]].<ref>{{Cite journal|last1=Summar|first1=Marshall L.|last2=Koelker|first2=Stefan|last3=Freedenberg|first3=Debra|last4=Le Mons|first4=Cynthia|last5=Haberle|first5=Johannes|last6=Lee|first6=Hye-Seung|last7=Kirmse|first7=Brian|date=2013|title=The incidence of urea cycle disorders|journal=Molecular Genetics and Metabolism|volume=110|issue=1–2|pages=179–180|doi=10.1016/j.ymgme.2013.07.008|issn=1096-7192|pmc=4364413|pmid=23972786}}</ref> [[Genetic disorder|Genetic defects]] in the enzymes involved in the cycle can occur, which usually manifest within a few days after birth.<ref name=":122">{{Cite book|title=BIOCHEMISTRY A Short Course|last1=Tymoczko|first1=John L.|last2=Berg|first2=Jeremy M.|last3=Stryer|first3=Lubert|publisher=W.H. Freeman and Company, New York|year=2013|isbn=978-1-4292-8360-1|pages=529}}</ref> The recently born child will typically experience varying bouts of [[vomiting]] and periods of [[lethargy]].<ref name=":122" /> Ultimately, the infant may go into a [[coma]] and develop [[brain damage]].<ref name=":122" /> New-borns with UCD are at a much higher risk of complications or death due to untimely [[Screening (medicine)|screening tests]] and [[Medical error|misdiagnosed]] cases. The most common misdiagnosis is [[neonatal sepsis]]. Signs of UCD can be present within the first 2 to 3 days of life, but the present method to get confirmation by test results can take too long.<ref name=":5" /> This can potentially cause complications such as coma or death.<ref name=":5">{{cite journal|last1=Merritt |first1=J. L. |last2=Brody |first2=L. L. |last3=Pino |first3=G. |last4=Rinaldo |first4=P. |date=2018 |title=Newborn screening for proximal urea cycle disorders: Current evidence supporting recommendations for newborn screening |journal=Molecular Genetics and Metabolism |volume=124 |issue=2 |pages=109–113 |doi=10.1016/j.ymgme.2018.04.006|pmid=29703588 |s2cid=13858458 }}</ref>

Urea cycle disorders may also be diagnosed in adults, and symptoms may include [[delirium]] episodes, [[lethargy]], and symptoms similar to that of a [[stroke]].<ref>{{Cite book|title=Genetic Disorders Sourcebook|last=Judd|first=Sandra|publisher=Omnigraphics|year=2010|isbn=978-0-7808-1076-1|pages=225}}</ref> On top of these symptoms, if the urea cycle begins to malfunction in the [[liver]], the patient may develop [[cirrhosis]].<ref name=":6" /> This can also lead to [[sarcopenia]] (the loss of muscle mass).<ref name=":6">{{Cite journal|last=Qiu|first=Jia|date=July 9, 2013|title=Hyperammonemia in cirrhosis induces transcriptional regulation of myostatin by an NF-κB–mediated mechanism|journal=Proceedings of the National Academy of Sciences of the United States of America|publisher=National Academy of Sciences|volume=110|issue=45|pages=18162–18167|jstor=23754730|doi=10.1073/pnas.1317049110|pmid=24145431|pmc=3831479|bibcode=2013PNAS..11018162Q|doi-access=free}}</ref> Mutations lead to deficiencies of the various enzymes and transporters involved in the urea cycle, and cause urea cycle disorders.<ref name=":0" /> If individuals with a defect in any of the six enzymes used in the cycle ingest [[amino acid]]s beyond what is necessary for the minimum daily requirements, then the ammonia that is produced will not be able to be converted to urea. These individuals can experience [[hyperammonemia]], or the build-up of a cycle intermediate.

=== Individual disorders ===
* [[N-Acetylglutamate synthase deficiency|N-Acetylglutamate synthase (NAGS) deficiency]]
* [[Carbamoyl phosphate synthetase I deficiency|Carbamoyl phosphate synthetase (CPS) deficiency]]
* [[Ornithine transcarbamoylase deficiency|Ornithine transcarbamoylase (OTC) deficiency]]
*  [[Citrullinemia|Citrullinemia type I]] (Deficiency of argininosuccinic acid synthase)
* [[Argininosuccinic aciduria]] (Deficiency of argininosuccinic acid lyase)
* [[Argininemia]] (Deficiency of arginase)
* [[Hyperornithinemia, hyperammonemia, homocitrullinuria syndrome|Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome]] (Deficiency of the mitochondrial ornithine transporter)<ref name=":4" /><ref>{{Citation|last1=Smith|first1=L. D.|title=Chapter 5: Urea cycle and other disorders of hyperammonemia|date=2017-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780128028964000043|work=Biomarkers in Inborn Errors of Metabolism|pages=103–123|editor-last=Garg|editor-first=Uttam|place=San Diego|publisher=Elsevier|language=en|doi=10.1016/b978-0-12-802896-4.00004-3|isbn=978-0-12-802896-4|access-date=2020-11-10|last2=Garg|first2=U.|editor2-last=Smith|editor2-first=Laurie D.}}</ref>

All urea cycle defects, except OTC deficiency, are inherited in an [[autosomal recessive]] manner. OTC deficiency is inherited as an [[X-linked recessive]] disorder, although some females can show symptoms. Most urea cycle disorders are associated with [[hyperammonemia]], however argininemia and some forms of argininosuccinic aciduria do not present with elevated ammonia.