A third of Wilson's disease diagnostic test involves measuring the level of copper in the liver. Consists of taking a sample of liver tissue (biopsy). It is one of the most effective ways to detect disease, but is more difficult. Other tests that may be used include: Measuring copper excreted in the urine daily (every 24 hours), measuring ceruloplastine’s ability to bind to some form of copper (Wilson's disease is low in) DNA tests.  Molecular genetic tests are not very effective in diagnosing Wilson's disease because of the large number of possible genetic mutations.

-Treatment for clinical symptoms of Wilson's disease:  Wilson's disease treatment goal is to remove excess copper and prevent its accumulation. Once you begin treatment, the disease stop evolution and many signs and symptoms are improving. But some problems require more time to improve. Other disorders - in particular, liver damage and certain neurological or psychological symptoms - are not fully reversible.

Chelated therapy
Chelated therapy is the use of chemicals that bind and remove metals and minerals from the body.

Penicillamine.
Penicillamine is the first drug approved for chelated copper for cure the clinical symptoms of Wilson's disease. Works by binding to copper and create a water-soluble complex that is excreted through urine.  Although an effective treatment, penicillamine can cause serious side effects, such as skin problems, bone marrow suppression, worsening of neurological symptoms and congenital defects. Penicillamine should not be managing people with kidney disease or those allergic to penicillin.People who follow treatment with penicillamine should consume vitamin B6 supplements, because the drug can cause a severe deficiency of this vitamin.



Trientina
A chelating agent is trientina that bind with copper and help remove it from the body. Since penicillamine is less toxic than many doctors recommend as a first line treatment, especially in people with neurological or hepatic symptoms.  Trientina also binds iron, and taking supplements rich in this mineral may reduce efficacy.

Zinc acetate
Acting differently than drugs chelate, zinc helps prevent copper absorption in stomach and small intestine. Zinc shows few side effects, but works slower than penicillamine and trientina. Is usually given as initial treatment only to pregnant women, people without symptoms of liver, or those who can not tolerate stronger medications. Doctors can alter the treatment of persons receiving penicillamine and zinc nitrate trientina once symptoms have improved. Zinc can also be used in combination with penicillamine in patients with neurological symptoms. People with Wilson's disease should follow medical treatment for life. Also, they should avoid foods rich in copper, such as liver, shellfish, mushrooms, nuts, chocolate, dried fruit, avocado.



Liver transplantation. In the case of patients with severe cirrhosis, fulminating hepatitis or other serious liver disease, liver transplantation may be the only treatment option.

-Prognosis:  If it’s not treated, Wilson's disease is always fatal.  With treatment, symptoms may continue to worsen for the first 6-8 weeks. After this period, clear improvements begin to be observed. However, it may take several years (2-5) for the treatment to achieve maximum efficiency in the brain and liver. Even if most patients do not regain the original level of functioning.  Patients with Wilson's disease must follow a certain form of treatment to prevent the rest of their life to increase the level of copper in the body. Discontinuation may lead to a relapse of the disease which is not reversible and can cause death.

Clinical symptoms of Wilson's disease: Regarding the people with Wilson disease, copper begins to accumulate in the liver soon after birth, but signs and symptoms rarely occur before the age of 5-6 years. Disease almost always becomes apparent before the age of 30 years, but symptoms can sometimes occur in old age. Accumulated copper may affect many organs and tissues, but most frequently are damaged liver and central nervous welfare payments. Symptoms of Wilson's disease include:

Liver problems: Because copper initially accumulates in the liver, most people shows signs of liver damage, including abdominal pain and yellow coloring of skin and cornea (jaundice).

Later, anemia and vomiting can occur with blood. Sometimes the disease progresses without obvious clinical symptoms of Wilson's disease until patients develop cirrhosis - irreversible liver damage that affects its function. At this stage, the signs and symptoms may include swelling of the abdomen (ascites) or legs (edema) and enlarged spleen (splenomegaly).

-Neurological problems: Approximately one third of patients with Wilson disease show neurological signs and symptoms such as tremors, muscle spasms, uncertain gait, and speech difficult and excessive salivation.

-Behavioral or psychological disorders: Wilson's disease can cause personality changes and inappropriate behavior. Children with this disorder are sometimes wrongly diagnosed with behavioral disorders because they misbehave or bad results at school.

-Eye disorders, kidney and bone: Many patients with Wilson's disease, even those who do not have other signs and symptoms, develop a yellowish-brown coloration characteristic around the cornea (Kayser-Fleischer ring). Caused by copper deposits, Kayser-Fleischer rings are frequently discovered during a routine ophthalmological. Wilson's disease can also affect kidney function and lead to brittle bones (osteoporosis). The disease can also lead to kidney stones.



-Diagnosis: Wilson's disease diagnosis can be made relatively easily by various tests. But as Wilson's disease is very rare and its main symptoms are very similar to those of hepatitis, alcoholic cirrhosis and other chronic liver diseases, diagnosis is often set later. Diagnosis is based on a combination of current symptoms and tests. Used tests can be performed in patients who have symptoms or not. It is important that the disease be found as quickly as to have liver damage may occur without any symptoms.



An easy way to diagnose Wilson's disease is to measure the level of glycoproteins found in blood, called ceruloplastina. Ceruloplastine can identify low levels of disease in approximately 80% of patients. This method is not effective in women who take birth control pills, are pregnant or children under 6 months.

Another test involves examining the eye to reveal a characteristic ring of copper stored in a membrane of the cornea (called the Kayser-Fleischer ring). This method is easily performed and is very effective in finding disease in patients who have symptoms. It is not as effective in people without symptoms (asymptomatic). This test is not sufficient to confirm this disease because some patients with liver disease may present the same results.

Wilson's disease is an inherited disorder that causes excessive copper accumulation in the body. It is also known as hepatolenticulary degeneration. Copper plays an important role in the harmonious development of nerves, bones, collagen and melanin. Normally, copper is absorbed from food, and excess is excreted through bile - substance produced in the liver and stored in the gallbladder.

When gall bladder evacuates its contents into the duodenum (first portion of small intestine), copper content in the ball crosses the gut with food digestion. In healthy people, copper is then discharged from the body through the stool.  In Wilson disease, copper does not pass the ball, but accumulate in the liver. As the level of copper in the liver increases, affected organ begins to allow its passage into the bloodstream. Copper is then stored in the body, especially the kidneys, brain and nervous system and eyes.  Wilson's disease affects about 1 in 30,000 to 100,000 people. Around one in 90 people is a carrier of Wilson's disease gene.  Clinical symptoms of Wilson's disease are fatal if not diagnosed and treated in time.



-Causes:  When you eat foods rich in copper (e.g.: liver, shellfish, peanuts, avocado, mushrooms), it is absorbed in the small intestine, reach the circulation where it binds to proteins and transported to the liver. The amount of copper used by the body is eliminated through the bile, a substance produced by the liver that helps digest fats.
In Wilson disease, a genetic mutation of chromosome 13 affects ATP7B gene, which interferes with transport of copper into bile. Gene is also involved in incorporating copper into ceruloplasmin, the protein that carries mineral by the bloodstream.

ATP7B gene lead to impaired improper disposal of copper, which accumulates in the liver, which can cause serious and sometimes irreversible damage. With excess copper during the "flows”, it begins to accumulate in other organs, especially in brain, eyes, kidneys and joints.  Although some ATP7B gene mutations occur spontaneously, most are transmitted from one generation to another. Wilson's disease is inherited as an autonomic recessive character, which means to develop the disease; the child must inherit two copies of the gene affectionate, one of the parent cation. If you receive only one copy of the abnormal gene you will not develop the disease but can transmit the gene becomes a carrier and its children.



-Risk factors for clinical symptoms of Wilson's disease:
If both parents are carriers of a defective gene copies, it shows a 25% chance of having a child with two normal genes, 50% have a child carrier of the gene (A single copy of the defective gene and one normal copy), and a 25% chance of having a child with two faulty genes will develop the disease. These opportunities remain unchanged for each task.  For this reason experts recommend that all children and all relatives of people with Wilson's disease to be tested to determine the disease.

Between all the clinical symptoms of Wilson's disease described in the anterior lines, there are many other signs. In the following lines, I'll try to explain all of them:


Skeletal bone damage:
• osteoporosis, osteomalacia, condrocalcinose;
• osteoarthritis, joint hiperlaxitation.
Eye damage:
• Kayser-Fleischer ring this: a brown or green ring at the edge of corneal languages;
• cataract in the sun-flower bright and colorful, visible only with slit lamp;
• Exotropic strabismus, optical neural;
• Night blindness.

Other common clinical symptoms of Wilson's disease are greenish nail color, arthropathy, and anemia.
Liver damage is common initial manifestation in children. Approximately 40-50% of patients present liver disease, psychiatric and neurological symptoms and signs.
-Diagnosis of Wilson's disease:
Laboratory studies in the diagnosis of Wilson's disease:
• Low level of serum copper (normal 80-168 mcg / dl);
• Low level of serum ceruloplasmin <20mg/dL (normal 20-60 mcg / dl);
• ceruloplasmin levels may be normal in women who have oral contraceptives and during pregnancy, can be dropped in aceruloplasmin, multiple sclerosis, Huntington's disease;
• increased urinary copper levels> 100mcg/24 hours (normal hours 10-80mcg/24);
• hypercalciuria and Fanconi syndrome with tubular acidosis secondary and / or to impaired renal aminoaciduria ;
• hyperparathyroidism;
• hemolytic anemia with negative Coombs test;
• abnormal transaminase levels.

-Imaging studies in diagnosing Wilson's disease:



-Radiology or absorptiometry (DEXA) indicates osteoporoses

-Computed tomography brain shows cerebral atrophy and hipoatenuation of putamen.

-MRI shows brain copper accumulation in the basal ganglia, thalamus, cerebellar nucleus, needle and white matter, with cortical atrophy, enlargement of ventricles.

-Echography transcranial highlights hiperecogenitation of lenticular nucleus and asymptomatic patients are more sensitive than MRI.

Other procedures used are Tc99 scan and NMR spectroscopy:
-Liver biopsy shows liver copper deposits increased by spectroscopic measurements, marking with histochemical rhodanina.
-Genetic analysis of ATP7B gene identification.
-Ophthalmic examination at the slit lamp for cataract evident in flower sun and Kayser-Fleisher ring.
-Histopathology shows brain tissue: Hollow degeneration, gliosis, copper deposits in the basal ganglia, Opalski cells, neuronal loss, liver tissue: diffuse accumulation of copper in the cytoplasm, macro and microsteatoza, glycogen nuclei, periportal inflammation, mononuclear infiltrates, lobular necrosis fibrosis and Mallory bodies in the deck. Installs late cirrhosis with regenerative nodules of different sizes.

Wilson disease treatment:
Drug treatment of Wilson's disease is based on metal chelating agents. D-penicillamine binds copper and form soluble complexes which are excreted in urine. This may cause reversible neurological signs, Kayser-Fleischer ring and cataract. Improve psychiatric symptoms, aminoaciduria, peptiduria and liver disease.



Adverse effects of D-penicillamine are allergic reactions, pruritus, headache, nausea and impaired lymphatic. Sometimes, hardware failure occurs. In these cases, treatment will be restarted with a low dose which will gradually higher thereafter.

Other side effects include: pemphigus, lipoid syndrome, bone marrow inhibition, delayed wound healing and teratogenicity. For pregnant women are contraindicated because of teratogenic effects for penicillamine-congenital malformations.

Metalothionine zinc acetate induces synthesis of intestinal cells, a substance which has a high affinity for copper and prevents its absorption. Copper is excreted in the stool with intestinal cells degenerate. Zinc acetate may be given pregnant.

Trientina binds copper and increases its urinary excretion.

In this article, I'd like to talk about Wilson's disease but also about clinical symptoms of Wilson disease. Wilson's disease is a neuro-degenerative disorder of copper metabolism. In 1912, Wilson first described as a family disease which associates neurological symptoms and cirrhosis. Wilson's disease involves loss of liver ability to remove copper by bile and its incorporation into cerulo-plasmin liver-transporter protein. As a result, copper accumulates in liver, brain, kidneys and corneas.

The disease mostly affects young patients, aged between eight and 20 years. Any person with liver disease medically unexplained recurrent neurological symptoms require investigation for Wilson's disease. Liver damage may have four manifestations: acute hepatitis, chronic acute hepatitis, fulminated hepatitis and cirrhosis. Repeated episodes of hepatitis may occur along the several years before the onset of neurological signs.

In final stage, all patients will develop cirrhosis. Fulminated hepatic damage can lead to sudden release of copper in the blood by installing hemolytic anemia, a serious condition of life if it’s not corrected promptly. Neurological manifestations may occur without liver disease and is presented in a variety of signs and symptoms, including: tremor, spasticity, rigidity or core. Once diagnosed, a treatment should be initiated immediately, even if the patient is asymptomatic. Penicillamine is the drug of choice.

-Pathogenesis and causes of Wilson disease: Wilson's disease is caused by pathological accumulation of copper in the body. Copper in the diet normally is filtered by the liver and eliminated in bile and then eliminated through the digestive tract of organisms. Sick people can not remove copper due to inherited mutations of ATP7B gene. When the storage capacity of copper is exceeded in the liver and liver necrosis occurs copper is released into the bloodstream and reach other organs susceptible to capture him: brains, kidneys and corneas.



ATP7B gene encodes a protein synthesis with the same name which favors transport copper to the liver where it is incorporated into ceruloplasmin. 95% of copper bound to ceruloplasmin serum. Serum ceruloplasmin levels in Wilson's disease is low, not by affecting synthesis apoceruloplasmin by copper, but the life of apoceruloplasmin decrease from 4-5 days to 4-5 hours in the absence of copper.
Wilson's disease is an autonomic recessive disease transmitted from genitals.



-Signs and clinical symptoms of Wilson's disease:
Wilson's disease first attacks the liver and central nervous system. Copper accumulation in hepatocytes cause acute hepatitis, chronic acute hepatitis, cirrhosis or fulminated hepatitis.
Clinical manifestations of liver damage include:

• hepatomegaly, splenomegaly;

• jaundice, ascites, peripheral edema, fatigue;

• tendency to prolonged bleeding and bruising (bruises).
Neurological signs include:

• Parkinson symptoms, rigidity, and bradykinesia;

• dysarthria, tremor at rest or activity, facial dystonia;

• disdiadocokinezia, shaky writing, inordinate, abnormal eye movements;

• Respiratory dyskinesia unusual cough;

• polyneuropathy.

Psychiatric signs:

• hyperkinetic behavior, irritability or anger;

• emotional lability, psychosis, anger, difficulty concentrating;

• abnormal behavior, personality changes, depression, schizophrenia.