Differences

Last edited on April 30, 2020

This shows you the differences between two versions of the page.

--- cl:wilsons-disease [on September 15, 2018]
+++ cl:wilsons-disease [on July 18, 2024] (current)
psychdb [Pathophysiology]
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 ====== Wilson's Disease =====
+{{INLINETOC}}
 ===== Primer =====
-**Wilson's Disease** is a rare autosomal recessive disorder that results in copper build up in the body. There are both neuropsychiatric and GI/hepatic signs and symptoms.
+**Wilson's Disease** (Wilson Disease) is a rare autosomal recessive disorder that results in copper build up in the brain and liver. There are both neuropsychiatric and GI/hepatic signs and symptoms.
-==== Prevalence ====
+== Epidemiology ==
-Wilson's disease occurs in about 1 in 30,000 people. Symptoms usually begin between the ages of 5 and 35 years. Males and females are equally affected.
+  * Wilson's disease occurs in about 1 in 30,000 people.
+  * Males and females are equally affected.
+  * The prevalence is higher in Japan.[([[https://pubmed.ncbi.nlm.nih.gov/33260258/|Yamaguchi, H., Nagase, H., Tokumoto, S., Tomioka, K., Nishiyama, M., Takeda, H., ... & Nozu, K. (2021). Prevalence of Wilson disease based on genome databases in Japan. Pediatrics International, 63(8), 918-922.]])]
+== Prognosis ==
+  * Symptoms usually begin between the ages of 5 and 35 years (average age of 17).
+== Comorbidity ==
+  * If detected early and treated appropriately, individuals can have normal health and a normal lifespan.
+  * In untreated cases, the disease is progressive and disease can occur within 5 to 10 years (from severe brain damage, liver failure).
+    * Severe hemolytic anemia can also be an unusual complication of Wilson’s disease.[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002091/|Sharma, S., Toppo, A., Rath, B., Harbhajanka, A., & Lalita Jyotsna, P. (2010). Hemolytic anemia as a presenting feature of wilson’s disease: a case report. Indian Journal of Hematology and Blood Transfusion, 26(3), 101-102.]])]
 ===== Symptoms =====
-  * Neuropsychiatric symptoms include [[neurology:approaches:tremors|tremors]], muscle stiffness, [[neurology:approaches:aphasia|aphasia]], personality changes, [[anxiety:home|anxiety]], and hallucinations. Psychiatric symptoms due to Wilson's disease are present in about 15% of patients.
+  * The clinical spectrum of liver disease can range from being asymptomatic to acute liver failure or cirrhosis
   * Hepatic/GI symptoms include vomiting, weakness, ascites, edema, jaundice, and jaundice-associated pruritis.
+  * Adults may have additional neuropsychiatric symptoms which can include:
+    * Neurologic symptoms such as[[neurology:approach-tremors|tremors]], muscle stiffness, and [[neurology:approach-aphasia|aphasia]]
+    * Psychiatric symptoms (present in about 15% of cases) such as personality changes, [[anxiety:home|anxiety]], hallucinations, psychosis, or depressive symptoms.
-===== Pathophysiology =====
-Wilson's disease is an autosomal recessive disorder. It is due to a mutation in the Wilson disease protein (ATP7B) gene.
+===== Pathophysiology =====
+  * Wilson's disease is an autosomal recessive disorder of copper metabolism in chromosome 13, due to a mutation in the Wilson disease protein (ATP7B) gene.
+  * Copper excretion by the liver is impaired in Wilson's disease
+    * The defective biliary excretion of copper causes copper accumulation in tissues, particularly in the brain (basal ganglia), liver, and cornea[([[https://www.cmaj.ca/content/196/1/E14|Chan, S. E., & Tran, A. M. (2024). Wilson disease in a 19-year-old female. CMAJ, 196(1), E14-E16.]])]
 ===== Investigations =====
-  * Serum ceruloplasmin level and 24-hour urinary copper excretion should be ordered in young patients presenting with tremor to rule out Wilson's
+  * In young patients presenting with [[neurology:approach-tremors|tremors]], one should always order:[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940372/#sec10title|Patil, M., Sheth, K. A., Krishnamurthy, A. C., & Devarbhavi, H. (2013). A review and current perspective on Wilson disease. Journal of clinical and experimental hepatology, 3(4), 321-336.]])]
-  * A [[neurology:investigations:neuroimaging:ct|CT head]] will often show signs of neurodegenerative disease
+    * Serum ceruloplasmin level (low, due to the shorter half-life of non–copper-bound ceruloplasmin)
+    * Total serum copper (low, since serum ceroplasmin is low)
+    * Free serum copper (elevated)
+    * 24-hour urinary copper excretion (universally elevated in untreated individuals)
+    * Ferritin levels (elevated)
+  * Liver biopsy will indicate elevated copper levels due to copper deposition
+  * Genetic testing for ATP7B gene variations can provide diagnostic confirmation if biochemical testing is not definitive
+==== Neuroimaging ====
+  * [[neurology:ct-scan|CT head]] will often show signs of atrophic changes in the basal ganglia, cortical, and cerebellar regions that mimics neurodegenerative disease.
+  * [[neurology:mri|MRI head]] will show increased signal in the basal ganglia and especially in the putamen
 ===== Physical Exam =====
-  * "Wing-beating" [[neurology:approaches:tremors|tremor]]
+  * Dysarthric speech is the most common neurological sign[([[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531649high|Dusek, P., Litwin, T., & Członkowska, A. (2019). Neurologic impairment in Wilson disease. Annals of Translational Medicine, 7(Suppl 2).]])]
-  * Kayser-Fleischer rings are seen on ophthalmoscopic examination by slit lamp
+  * Patients will often appear jaundiced
+  * On gait exam, there is typically an ataxic gait
+  * A "wing-beating" [[neurology:approach-tremors|tremor]] is commonly present as well
+  * Kayser-Fleischer rings, which represent copper deposits in the Descemet membrane of the cornea, are seen on ophthalmoscopic examination by slit lamp.
+    * Kayser-Fleischer rings are a pathognomonic finding of Wilson disease but can be absent in around 50% of patients with Wilson disease.[([[https://pubmed.ncbi.nlm.nih.gov/22340672/|European Association For The Study Of The Liver. (2012). EASL clinical practice guidelines: Wilson’s disease. Journal of hepatology, 56(3), 671-685.]])]
+    * Patients should be referred to an ophthalmologist for assessment.
+===== Treatment =====
+<alert type="info" icon="fa fa-book fa-lg fa-fw">
+See also: **[[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022881/|Litwin, T. et al. (2018). Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment. Therapeutic advances in psychopharmacology, 8(7), 199-211.]]**
+</alert>
+  * Treatment for stable symptomatic Wilson disease includes copper-chelating agents such as D-penicillamine or trientine.
+    * Asymptomatic patients may be treated with lower doses of copper-chelating agents or with zinc salts that lower intestinal copper absorption.
+    * Lifelong maintenance therapy and clinical monitoring is required when patients are on chelating agents or zinc.
+  * Patients with existing cirrhosis with synthetic dysfunction do not benefit from copper chelators
 ===== Resources =====
-==== Case Reports ====
+<WRAP group>
+<WRAP quarter column>
+== For Patients ==
+</WRAP>
+<WRAP quarter column>
+== For Providers ==
+  * [[https://www.cmaj.ca/content/196/1/E14|Chan, S. E., & Tran, A. M. (2024). Wilson disease in a 19-year-old female. CMAJ, 196(1), E14-E16.]]
+  * **[[https://www.nature.com/articles/s41572-018-0018-3|Członkowska, A. et al. (2018). Wilson disease. Nature reviews Disease primers, 4(1), 1-20.]]**
+</WRAP>
+<WRAP quarter column>
+== Articles ==
+</WRAP>
+<WRAP quarter column>
+== Research ==
   * [[https://www.sciencedirect.com/science/article/pii/S0924933813769852|Aljukić, N., Sutović, A., Avdić, L., Pajević, I., & Hasanović, M. (2013). 2080–A neuropsychiatric presentation of Wilson's disease-Case report. European Psychiatry, 28, 1.]]
+</WRAP>
+</WRAP>