Editing Wilson's disease (section)

==Signs and symptoms==
The main sites of copper accumulation are the [[liver]] and [[Human brain|brain]]. Consequently, liver disease and neuropsychiatric symptoms are the main features that lead to diagnosis.<ref name=Ala>{{cite journal |vauthors=Ala A, Walker AP, Ashkan K, Dooley JS, Schilsky ML |title=Wilson's disease |journal=Lancet |volume=369 |issue=9559 |pages=397–408 |year=2007 |pmid=17276780 |doi=10.1016/S0140-6736(07)60196-2|s2cid=24663871 }}</ref> People with liver problems tend to come for medical attention earlier (generally as children or teenagers) than those with neurological and psychiatric symptoms, who tend to be in their 20s or older. Some are identified only because relatives have been diagnosed with Wilson's disease; many of these, when tested, turn out to have been experiencing symptoms of the condition but have not received a diagnosis.<ref name=Merle2007>{{cite journal |vauthors=Merle U, Schaefer M, Ferenci P, Stremmel W |title=Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study |journal=Gut |volume=56 |issue=1 |pages=115–20 |year=2007 |pmid=16709660 |doi=10.1136/gut.2005.087262 |pmc=1856673 }}</ref>

===Liver disease===
Liver disease may present itself as [[tiredness]], [[jaundice]], increased bleeding tendency or confusion (due to [[hepatic encephalopathy]]), and [[portal hypertension]].<ref>{{Cite web |title=Wilson's disease - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/wilsons-disease/symptoms-causes/syc-20353251 |access-date=2022-10-05 |website=Mayo Clinic |language=en}}</ref> The last, a condition in which the pressure in the [[portal vein]] is markedly increased, leads to [[esophageal varices]] (distended veins in the [[esophagus]] that may bleed in a life-threatening fashion) as well as enlargement of the spleen ([[splenomegaly]]) and accumulation of fluid in the abdominal cavity ([[ascites]]). On examination, signs of chronic liver disease such as [[spider angioma]]ta (small distended blood vessels, usually on the chest) may be observed. [[Chronic active hepatitis]] has already caused [[cirrhosis]] of the liver in most patients by the time they develop symptoms. While most people with cirrhosis have an increased risk of [[hepatocellular carcinoma]] (liver cancer), this risk is relatively low in Wilson's disease.<ref name=Ala/>

About 5% of all people are diagnosed only when they develop [[fulminant]] [[acute liver failure]], often in the context of [[hemolytic anemia]] (anemia due to the destruction of red blood cells). This leads to abnormalities in protein production (identified by [[Coagulopathy|deranged coagulation]]) and metabolism by the liver. The deranged protein metabolism leads to the accumulation of waste products, such as [[ammonia]], in the bloodstream. When these irritate the brain, patients develop [[hepatic encephalopathy]] – a serious condition that causes confusion, coma, seizures and, finally, life-threatening [[Cerebral edema|swelling of the brain]]).<ref name=Ala/>

===Neuropsychiatric symptoms===
[[File:Wilson's Disease 5.jpg|thumb|Girl with Wilson's disease showing neurological symptoms]]
About half of the people with Wilson's disease have neurological or psychiatric symptoms. Most initially have mild cognitive deterioration and clumsiness, as well as changes in behavior. Specific neurological symptoms usually then follow, often in the form of [[parkinsonism]] (lead-pipe or cogwheel rigidity, [[bradykinesia]], and postural instability<ref name=Lorincz2010 />) with or without a typical hand [[tremor]], masked facial expressions, slurred speech, [[ataxia]] (lack of coordination), or [[dystonia]] (twisting and repetitive movements of part of the body). [[Seizure]]s and [[migraine]] appear to be more common in Wilson's disease.<ref name=Ala/> A characteristic tremor described as "wing-beating tremor" is encountered in many people with Wilson's; this is absent at rest but can be provoked by abducting the arms and flexing the elbows toward the midline.<ref>{{cite book|last=Pagonabarraga|first=J|title=Practical Neurology|date=2012|publisher=Wolters Kluwer/Lippincott Williams & Wilkins Heath|location=Philadelphia|isbn=978-1451142631|page=282|edition=4th|author2=Goetz, C |editor=Biller, J}}</ref>

Cognition can also be affected in Wilson's disease, in two non-mutually exclusive categories: [[frontal lobe disorder]] (may present as [[impulsivity]], impaired judgement, [[promiscuity]], [[apathy]], and [[executive dysfunction]] with poor planning and decision-making) and [[subcortical dementia]] (may present as slow thinking, memory loss, and [[executive dysfunction]], without signs of [[aphasia]], [[apraxia]], or [[agnosia]]). These cognitive involvements are thought to be related and closely linked to psychiatric manifestations of the disease.<ref name=Lorincz2010>{{cite journal | author=Lorincz MT | year=2010 | title=Neurologic Wilson's disease | journal=Annals of the New York Academy of Sciences | volume=1184 | issue=1 | pages=173–87 | doi=10.1111/j.1749-6632.2009.05109.x | pmid=20146697 | bibcode=2010NYASA1184..173L | hdl=2027.42/78731 | s2cid=2989668 | url=https://deepblue.lib.umich.edu/bitstream/2027.42/78731/1/j.1749-6632.2009.05109.x.pdf | hdl-access=free }}</ref>

Psychiatric problems due to Wilson's disease may include behavioral changes, [[clinical depression|depression]], [[anxiety disorders]], and [[psychosis]].<ref name=Ala/> Psychiatric symptoms are commonly seen in conjunction with neurological symptoms and are rarely manifested on their own. These symptoms are often poorly defined and can sometimes be attributed to other causes. Because of this, diagnosis of Wilson's disease is rarely made when only psychiatric symptoms are present.<ref name=Lorincz2010 />

=== Other organ systems ===
[[File:Kayser-Fleischer ringArrow.jpg|thumb|A brown ring on the edge of the iris ([[Kayser–Fleischer ring]]) is common in Wilson's disease, especially when neurological symptoms are present.]]
Medical conditions have been linked with copper accumulation in Wilson's disease:
* '''Eyes:''' [[Kayser–Fleischer ring]]s (KF rings) may be visible in the [[cornea]] of the eyes, either directly or on [[slit lamp]] examination, as deposits of copper form a ring around the cornea. This is due to copper deposition in [[Descemet's membrane]]. These rings can be either dark brown, golden, or reddish-green, are 1 to 3mm wide, and appear at the corneal limbus. They do not occur in all people with Wilson's disease, and may be seen in people with chronic [[cholestasis]].<ref name="Pandey">{{cite journal|url=https://www.ncbi.nlm.nih.gov/books/NBK459187/|title=Kayser-Fleischer Ring|date=21 June 2022|last1=Pandey|first1=Nivedita|last2=John|first2=Savio|access-date=30 November 2022|publisher=StatPearls Publishing|location=Treasure Island, Florida|journal=StatPearls|pmid=29083643}}</ref><ref name="Roberts2008">{{cite journal|last1=Roberts|first1=Eve A.|last2=Schilsky|first2=Michael L. |title=Diagnosis and treatment of Wilson disease: An update|journal=Hepatology|volume=47|issue=6|year=2008|pages=2089–2111|doi=10.1002/hep.22261|doi-access=free|pmid=18506894}}</ref> Wilson's disease is also associated with sunflower [[cataract]]s exhibited by brown or green pigmentation of the anterior and posterior lens capsule.<ref>{{cite book |last=Yanoff |first=Myron|author2=Jay S. Duker |title=Ophthalmology|year=2008|publisher=Mosby|location=Edinburgh|isbn=978-0323057516 |pages=411|edition=3rd}}</ref> Neither causes significant visual loss.<ref name=Ala/> KF rings occur in approximately 66% of diagnosed cases (more often in those with neurological symptoms rather than with liver problems).<ref name=Merle2007/>
* '''Kidneys:''' [[renal tubular acidosis#Type 2-Proximal RTA|renal tubular acidosis]] (Type 2), a disorder of [[bicarbonate]] handling by the [[proximal tubule]]s leads to [[nephrocalcinosis]] (calcium accumulation in the kidneys), a weakening of bones (due to calcium and phosphate loss), and occasionally [[aminoaciduria]] (loss of essential [[amino acid]]s needed for protein synthesis).<ref name=Ala/>
* '''Heart:''' [[cardiomyopathy]] (weakness of the heart muscle) is a rare but recognized problem in Wilson's disease; it may lead to [[heart failure]] (fluid accumulation due to decreased pump function) and [[cardiac arrhythmia]]s (episodes of irregular and/or abnormally fast or slow heart beat).<ref name=Ala/>
* '''Hormones:''' [[hypoparathyroidism]] (failure of the [[parathyroid gland]]s leading to low calcium levels), [[panhypopituitarism]] (leading to decreased production of hormones from the pituitary gland), [[infertility]], and [[recurrent miscarriage]].<ref name=Ala/><ref name="Roberts 2023">{{cite journal |last1=Roberts |first1=Eve A. |last2=Schilsky |first2=Michael L. |title=Current and Emerging Issues in Wilson's Disease |journal=New England Journal of Medicine |date=7 September 2023 |volume=389 |issue=10 |pages=922–938 |doi=10.1056/NEJMra1903585|pmid=37672695 |s2cid=261581755 }}</ref>
*'''Musculoskeletal:''' Arthritis and thinning of the bones ([[osteopenia]] or [[osteoporosis]]).<ref name="Roberts2003" />
*'''Fingers:''' [[Blue nails]], or more formally Azure Lunula, is seen as a blue colouring fading proximally. 
<gallery widths="200" heights="200">
*'''Fingers:''' [[blue nails]] 
File:Sunflower cataract.jpg|Sunflower cataract and thick KF ring of a 40-year-old male with Wilson's disease and decompensated [[chronic liver disease]]
File:KF ring 1.jpg|Diffuse illumination of cornea
File:KF ring 2.jpg|Copper deposition on corneal Descemet's membrane
</gallery>