Wilson’s Disease By: Molly Roemer

Meet Tommy A 12 year old boy named Tommy from Eastport, Maine was brought in to his family doctor for a check-up because he was having problems with his speech, swallowing, and he seemed to be losing coordination (1). He also had been feeling more tired than usual and seemed to be losing weight (1). Tommy’s mom was worried about these signs and also mentioned that Tommy loved to play soccer and had always been an active boy. However, Tommy had been wanting to stay home from practice and would fall asleep after coming home from school. After the initial examination, blood and urine tests showed that Tommy had anemia, low white blood cell and platelet count, and high levels of amino acids, protein, uric acid, and carbohydrates in the urine (1). The doctor also noticed that Tommy’s eyes had a brownish-gold ring around the irises (1,2). Tommy loved shellfish and ate it often, his favorites being lobster, shrimp, and clams.

Diagnosis: Wilson’s Disease Genetic disorder with a mutation on the gene that codes for ATP7B (1,2). Autosomal recessive mutation (both parents must pass onto offspring)

Diagnosis: Wilson’s Disease Copper cannot be excreted into the bile by the liver so it builds up in the liver, brain, eyes, and other organs Over time causes organ damage Diagnosed by: Medical/ family history Physical exam Blood, urine tests Liver biopsy Imaging tests (MRI, CT)

Symptoms: Wilson’s Disease Kayser-Fleischer ring (brownish-gold ring around iris in the eye) Problems with the liver and CNS: nausea, vomiting, edema, spider angiomas, jaundice, muscle cramps and stiffness, arthritis, osteoporosis, tremors, personality changes, depression, anxiety, psychosis Symptoms worse in individuals diagnosed later in life

Symptoms: Wilson’s Disease More serious complications include (1): Cirrhosis Kidney damage Nervous system problems Liver cancer Liver failure Death

Copper Found in all body tissues as either Cu1+ or Cu2+ High amounts found in shellfish, liver, mushrooms, nuts, eggs, and chocolate Mainly stored in the liver, bound to metallothionein When in use, functions as an enzyme cofactor and is important for iron use, synthesis of collagen, pigment production, and neurotransmitter production Regulated and excreted into the bile by the liver

Normal Conditions of Copper Use Excretion occurs through the ATPase ATP7B 1. ATP7B transports Cu1+ across the trans-Golgi network membrane and into the Golgi network 2. Cu1+ is incorporated into ceruloplasmin and other cuproenzymes

Excretion of Copper When in Excess & ATP7B’s Role 1. ATP7B moves to the canalicular membrane to facilitate the transport of copper 2. Copper is then moved from the vesicles across the canalicular membrane using murr1 (a copper chaperone) 3. Copper is then moved to the bile duct so that it can be excreted in the bile and eventually the feces ATP7B’s movement to the canalicular membrane from the trans- Gogli network is associated with a kinase-dependent phosphorylation (This increases its response to elevations in copper within the cell)

Tommy and Wilson’s Disease ATP7B does not work properly to transport copper into the bile, so over time and depending on the amount of copper consumed, there is a build-up of copper because it is not excreted. Builds up in the liver but also leaks out into the blood in an unbound form. Accumulates in organs, especially the brain, kidneys, and cornea of the eyes Tommy was most likely experiencing a build-up of copper in these organs Luckily, Tommy was diagnosed and treated. If he follows his treatment plan, he’ll be able to live a happy and good life

Let’s THINK! 1. Is there a difference between Wilson’s disease and a copper toxicity? If so, what makes Wilson’s disease different?

Let’s THINK! 2. Wilson’s disease is due to a mutation in the gene coding for ATP7B so it is present a birth (2). Do you think that the symptoms of Wilson’s disease would be evident when the child is an infant or when the child is older? Can you name some reasons as to why that would be the case?

Let’s THINK! 3. Understanding more about Wilson’s disease, what do you think would be possible treatments? How long does a person with Wilson’s disease need to continue their treatment? Does diagnosis age make a difference in the treatment?

Let’s THINK! 4. Can you think of any environmental precautions a person with Wilson’s disease should be aware of and avoid?

References 1. National Institute of Diabetes and Digestive and Kidney Diseases. Wilson Disease. Available at: http://www.niddk.nih.gov/health-information/health-topics/digestive-diseases/wilson-disease/Pages/facts.aspx. Accessed August 3, 2015. 2. Gropper SS, Smith JL. Advanced Nutrition and Human Metbolism. 6th ed. Belmont, CA: Wadsworth Cengage Learning; 2013. 3.Google.com. Wilson’s Disease. Available at: https://sites.google.com/site/wilsonsdiseaseferguson33/images. Accessed August 3, 2015. 4. Flipper.diff.org. Wilson’s disease. Available at: http://flipper.diff.org/app/items/993. Accessed August 3, 2015.

Emilee’s Story: https://www.youtube.com/watch?v=NLWuegkn17c 3 minutes long