Copper ion is good for the body; but what about Wilson disease?

When Harry was admitted to the emergency unit at the teaching hospital, little did his parents knew what they were in for, after several test had been conducted on the 22 years old Harry, the doctor came up with the conclusion that the whole family should go for a genetic testing. They all agreed, and after the test, it was discovered that the parents were carriers of mutated (changed) Wilson disease protein (ATP7B) gene which is a gene responsible for balancing copper (a trace mineral to be talk about latter) level in the body system by eliminating it's excess into the plasma and the bile so that it can get out of the body.

Their son Harry had inherited the affected copies of these genes from each of the parent and there they are in the hospital.

The symptoms they first noticed was that Harry's behavior suddenly changed, he had complained severally that he see things unexplainable, and when he asked his colleagues at office if they had seen same, their response wasn't in affirmation. He had severally complained that he normally experience muscle contraction and at times stiffness of muscles. The last straw that broke the camel's back was when he began to complain about migraine, coupled with slurred speech. That was when he was taken to the hospital.

At the hospital, there the doctor discovered that Harry had been manifesting neuropsychiatric symptoms peculiar to Wilson disease.

The laboratory test results show that the level of copper in his urine was higher than normal which is expected to be within 20–50 μg within 24 hours range. Another test the doctor recommended for him was a cerebral imaging (MRI) which was found to be abnormal. In the MRI scan, Hyperintensity (bright signals) in the part of the brain known as basal ganglia was observed. It is this part of the brain that the disease do affect ( basal ganglia is known to coordinate voluntary motor movement, cognition, habit learning and the movement of eye ). The doctor been convinced of the condition decided not to carry out liver function test and liver biopsy on Harry. Carrying out liver function test would have further shown the damages in the liver, but after the doctor had conducted genetic testing, on the parents, he decided not to proceed further with any other test.

MRI scans showing hyperintensities :CC BY 2.0

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Importance of copper in the body and Pathophysiology of Wilson disease.

As important as copper is in the body system, it accumulation is deadly. For instance, copper is required for absorption of iron from the intestines and ease iron metabolism. It's important for the production of hemoglobin and red blood cells in the bone marrow ( it produce blood cells). Copper is also essential in the connective tissue as it helps in the synthesis of collagen a structural protein present in the skin.

Copper plays active role in the Central Nervous System in two major ways:

• It is required in the synthesis of dopamine and norepinephrine, the two chemicals that are required for the transmission of nerve signals.
• Copper is also needed for the deposition of myelin sheath around the nerve cells.

Liver needs copper before it can release cholesterol from itself.

Now looking at the highlighted role of copper in the body is it not good then to have it in abundance in the body ? ,but the answer is no, because there is a recommended dietary allowance daily for different age group and gender,

for instance, an adult male and female should not take more than 900 μg/day, children between the ages of 1-3 years, 340 mcg, those that are between 4-8 years old, 440 mcg/day; 9-13 years old, 700 mcg/day; 14-18 years old 890 mcg/day.

Source

Importance of copper to the body can't be undermine as it has been stated above, it also act as a cofactor for some enzymes like cytochrome c oxidase, tyrosinase, superoxide dismutase,
ceruloplasmin, and dopamine β-hydroxylase.

After entry of copper into the body through the digestive tract, a transporting system carry it into the cells where some of it is binded to metallothionein a low molecular weight protein, while some part of the copper is carried by an antioxidant protein (ATOX1) to trans-Golgi network.

However, when copper concentration is in excess, an enzyme called ATP7A release it into the liver through the portal vein. The liver cells contain some protein such as CMT1 and metallothionein, but ATOX1 target and deliver copper to ATP7B in the liver. ATP7B then connects copper and ceruloplasmin [a copper carrying protein which catalyze the oxidation of iron ii to iron iii ] together and get copper released into the blood stream, and releasing excess into the bile.

The two function of ATP7B in connecting copper to ceruloplasmin and removing copper excess into the bloodstream are damaged in Wilson disease, there is accumulation of copper in the liver tissue, but ceruloplasmin secretion is unabated but lack copper so the ceruloplasmin is quickly degraded to the bloodstream.

Brief of it's genetics

ATP7B which is Wilson disease gene is one of the several genes identified with a chromosome 13 [ part of the 23 pairs of chromosome present in human], it is well shown in the liver, placenta and kidney. It's mutation has been connected with 90% most of the disease. 60% of reported cases of the has been linked to inheritance of two mutated copies of the gene, while 30% has been attributed to inheritance of just one abnormal copy while 10% of cases can't even be linked with the mutation.

This disease is not popular in most population, as it affects few individuals in a large population. Also, the type varies from region to region for instance, the H1069Q mutation, is popular in the western part of the globe while the R778L is peculiar to the Eastern part of the globe especially in the China.

The H1069Q mutation is when the amino acid histidine is been replaced by another amino acid called glutamine at a position 1069 in the protein sequence, while in the R778L, arginine is been replaced by leucine at position 778 in the protein sequence.

This condition is passed to the offspring in what is refered to as autosomal recessive pattern Been explained in the introduction, both parents must be carrier of the mutated gene before it can be inherited. Some people were reported not to have a family history of the disease. Those carrying just one disrupted gene are refered to as heterozygotes and their case may be said to be medically unimportant in copper metabolism abnormalities.

Wilson disease symptoms.

Symptoms that could be seen if brain is the part affected are migraine, slurred speech, imbalace gait, uncontrollable movement of the body, seizures. Though not only brain is the only part affected, liver is not left out. Symptoms that could be noticed when it affects liver are vomiting, weakness, leg swelling, yellow skin, fluid accumulation in the abdomen as well as itchiness.

The symptoms discussed above are not the only one that could be seen in a fellow suffering from Wilson disease. Several part of the body could also be affected as well. Like i earlier stated, that it's a disease that resulted from the inability of a mutated Wilson disease protein (ATP7B) gene from removing accumulated copper minerals from the body. Symptoms depends on the part of the body affected.

Some other part of the body which shows indication of this disease are the following:

• Eyes: In the part of the cornea of eyes is the Kayser–Fleischer rings (KF rings). The ring encircle the Iris of the eye ( coloured part of the eyes). This is as a result of copper deposit. Also, this disease is associated sunflower cataract which is shown by green or brown pigmentation of the lens capsule.

• Heart: Cardiomyopathy which is the weakness of the heart muscle is not really common in Wilson disease but it can't be ruled out as well. Cardiomyopathy has been recognized as one of the problem associated with Wilson disease. This may leads to irregular heartbeat or heart failure.

• Kidneys: Wilson disease is also associated with renal tubular acidosis, a condition in which proximal tubules present in the nephron a functional unit of the kidney is unable to properly handle the exchange of hydrogen ion for bicarbonate a condition that now result at calcium accumulation in the kidney, in short it leads to kidney stone and abnormal excretion of amino acid in the urine.

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Wilson disease could be difficult to be diagnosed because it symptoms is not only peculiar to it, other liver diseases like hepatitis present similar symptoms also, the changes in behavior that appears gradually may also be hard to connect it to Wilson disease. Several test combination and symptoms observed do help the doctor to make diagnosis. Some of the test used to make diagnosis has been stated in the introductory narration of this write up.

Other test that could be performed are the determination of the level of ceruloplasmin in the blood and copper level in the blood. Another test is to check for the presence of Kayser-Fleischer rings in the eyes. Also the presence of sunflower cataract is checked too by the ophthalmologist

Carrying out biopsy which involves examination of the liver for excess copper in the liver tissue could be carried out too.

Genetic testing as mentioned in the introduction will help the doctor to know the genetic mutation which leads to the disease, and it will help the doctor to screen other members of the family and treat them too before manifestation of the disease in them too.

Treatment:

Mostly, people suffering are been advised to stay clear off copper containing food such as, dried fruit, sesame oil and it seed, chocolate, mushroom and shellfish. Also the the doctor may recommend taking chelating agent which have a bidding site for copper and it's consumption prompt the body organs to release the consumed copper into the bloodstream. The copper is then been filtered by the kidney from where it is excreted out in the urine.

Treatment may also include prevention of copper from storing up again. But when there is serious liver damage, liver transplant may be required.

After normalcy has been restored, zinc in form of zinc acetate known as Galzin may be taken in place of previous chelators to ensure stability in the level of copper in the body. Reason for using Zinc is because it activate a protein in the cells present at the gut which binds copper and prevent it's from being absorbed and transported into the liver. This protein is called metallothionein

Conclusion

Wilson disease is an autosomal recessive condition, it is inherited from parents and in few cases not. When detected early, it may be treated and be less stressful in handling. I think intending couples should get themselves screen so as to know their status. Also, consumption of copper should be within the daily permissible limit.

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References

eurowilson.org/en/living/guide/diagnostic/index

mayoclinic.org/diseases-conditions/wilsons-disease/symptoms-causes

wikipedia.org/wiki/Wilson%27s_disease

webmd.com/vitamins/ai/ingredientmono-902/coppe

healthline.com/health/wilsons-disease#cause-and-risk

medicalnewstoday.com/articles