INTRODUCTION:

“If I have belief that I can do As early as 1935, copper was found to be essential for animals but only recently have researchers shown that it is required for humans.¹ Copper is part of several important enzymes called cuproproteins.² Copper absorbed from the intestinal tract is carried chiefly to the liver and bone marrow. In the liver it is incorporated into a copper-protein complex called ceruloplasmin which then circulates in the blood stream. Cuproprotein enzymes are needed for the proper utilization of iron and for the manufacture of hemoglobin and red blood cells in the bone marrow. Copper deficiency in humans is rare.¹Toxicity from dietary copper is encountered in humans only in Wilson's disease, a hereditary metabolic disorder in which copper accumulates in body tissues.³

Wilson disease is a genetic disorder in which large amounts of copper build up in the liver and brain. Wilson's disease causes liver damage, which can be slowly progressive or acute and very severe. It can also cause brain and nervous system damage, which can lead to psychiatric and neuromuscular symptoms.

Wilson's disease can be fatal, but is often very responsive to medical treatment, especially if it is diagnosed before serious illness develops.⁴

Copper is a trace mineral that our bodies need in small amounts. Most people get a lot more copper from food than they need. However, most people are also able to get rid of the excess copper. People with Wilson's disease cannot excrete the excess copper because of a defective copper transporting protein. The liver of a person who has Wilson's disease does not release copper into bile as it should. As a result, copper begins to build up in the liver right after birth and eventually damages this organ. When the liver can no longer hold the excess copper, the mineral goes into the bloodstream. It travels to other organs and may damage the brain, red blood cells, central nervous system, kidneys, and eyes.⁴

It is named after Samuel Alexander Kinnier Wilson (1878-1937), the British neurologist who first described the condition in 1912.⁵

What is Wilson’s Disease?

Wilson disease is a genetic disorder that is fatal unless detected and treated before serious illness from copper poisoning develops. Wilson disease affects approxi-mately one in 30,000 people worldwide. The genetic defect causes excessive copper accumulation in the liver or brain.⁶

Small amounts of copper are as essential as vitamins. Copper is present in most foods and most people have much more copper than they need. Healthy people excrete copper they don't need but Wilson disease patients cannot.⁶

Copper begins to accumulate immediately after birth. Excess copper attacks the liver or brain, resulting in hepatitis, psychiatric, or neurologic symptoms. The symptoms usually appear in late adolescence. Patients may have jaundice, abdominal swelling, vomiting of blood, and abdominal pain. They may have tremors and difficulty walking, talking and swallowing. They may develop all degrees of mental illness including homicidal or suicidal behavior, depression, and aggression. Women may have menstrual irregularities, absent periods, infertility, or multiple miscarriages. No matter how the disease begins, it is always fatal if it is not diagnosed and treated.⁶

Incidence

Wilson's disease occurs in one out of every 30,000 people. In most cases, it is inherited. A person must get two malfunctioning genes – one from each parent – in order to develop the disease. People with only one malfunctioning gene will never have symptoms and do not need treatment. However, they can pass the disease on to their children. Some cases of Wilson's disease are not inherited. In these cases, the cause of the gene defect is unknown. The only known risk factor for Wilson's disease is a family history of the disease.⁷

Some cases of Wilson's disease are not inherited. In these cases, the cause of the gene defect is unknown. The only known risk factor for Wilson's disease is a family history of the disease.⁷

CAUSES

Wilson disease is a rare inherited disorder. If both parents carry an abnormal gene for Wilson disease, there is a 25% chance in each pregnancy that the child will have the disorder.⁸

Wilson's disease is inherited as an autosomal recessive trait, which means that to develop the disease you must inherit two copies of the defective gene, one from each parent. If you receive only one abnormal gene, you won't become ill yourself, but you're considered a carrier and can pass the gene to your children.⁹

To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. These disorders are usually passed on by two carriers. Their health is rarely affected, but they have one mutated gene (recessive gene) and one normal gene (dominant gene) for the condition. Two carriers have a 25 percent chance of having an unaffected child with two normal genes (left), a 50 percent chance of having an unaffected child who also is a carrier (middle), and a 25 percent chance of having an affected child with two recessive genes (right)⁹

Wilson disease causes the body to take in and keep too much copper. The copper deposits in the liver, brain, kidneys, and eyes. The copper deposits cause tissue damage, tissue death, and scarring, which causes the affected organs to stop working correctly.⁹

This condition is most common in eastern Europeans, Sicilians, and southern Italians, but it may occur in any group. Wilson disease typically appears in people under 40 years old. In children, the symptoms begin to show by age 4.⁹

Signs And Symptoms

Hepatic dysfunction is the presenting feature in more than half of patients. Although the condition may manifest as acute hepatitis, the 3 major patterns of hepatic involvement are as follows:

v Chronic active hepatitis

v Cirrhosis (the most common initial presentation)

v Fulminant hepatic failure¹⁰

Signs of Fulminant Hepatic Failure Include the Following:

· Ascites and prominent abdominal veins

· Spider nevi

· Palmar erythema

· Digital clubbing

· Hematemesis

· Jaundice

· Neuropsychiatric features

Most patients who present with neuropsychiatric manifestations have cirrhosis. The most common presenting neurologic feature is asymmetric tremor, which is variable in character and may be predominantly resting, postural, or kinetic.¹⁰

Frequent early symptoms include the following:

· Difficulty speaking

· Excessive salivation

· Ataxia

· Masklike facies

· Clumsiness with the hands

· Personality changes¹⁰

Late manifestations (now rare because of earlier diagnosis and treatment) include the following:

· Dystonia

· Spasticity

· Grand mal seizures

· Rigidity

· Flexion contractures¹⁰

Psychiatric features (10-20% of patients) include the following:

· Emotional lability

· Impulsiveness

· Disinhibition

· Self-injurious behavior

· Psychiatric abnormalities associated with Wilson disease has been divided into the following 4 basic categories:

· Behavioral

· Affective

· Schizophrenic-like

· Cognitive¹⁰

Musculoskeletal Manifestations

· The arthropathy of Wilson disease is a degenerative process that resembles premature osteoarthritis

· Symptomatic joint disease usually arises late in the course of the disease, frequently after age 20 years

· The arthropathy generally involves the spine and large appendicular joints (eg, knees, wrists, hips)

· Osteochondritis dissecans, chondromalacia patellae, and chondrocalcinosis have also been described¹⁰

Hematologic and Renal Manifestations

· Coombs-negative acute intravascular hemolysis (10-15%)

· Urolithiasis

· Hematuria

· Kayser-Fleischer rings

· Formed by the deposition of copper in the Descemet membrane in the limbus of the cornea

· The color may range from greenish gold to brown

· Well-developed rings may be readily visible to the naked eye or with an ophthalmoscope set at +40

· When not visible to the unaided eye, the rings may be identified using slit-lamp examination or gonioscopy

· Observed in up to 90% of individuals with symptomatic Wilson disease and almost invariably present in those with neurologic manifestations

· No longer considered pathognomonic of Wilson disease unless accompanied by neurologic manifestations, as they may also be observed in patients with chronic cholestatic disorders¹⁰

Additional Meanifestations

· Skeletal abnormalities (eg, osteoporosis, osteomalacia, rickets, spontaneous fractures, polyarthritis)

· Cardiac manifestations (eg, rhythm abnormalities, increased autonomic tone)

· Skin pigmentation and a bluish discoloration at the base of the fingernails (azure lunulae)¹⁰

DIAGNOSIS

Considerations in the workup of Wilson disease are as follows:

· Serum ceruloplasmin levels are less than 20 mg/dL (reference range, 20-40 mg/dL) in approximately 90% of all patients with Wilson disease

· The urinary copper excretion rate is greater than 100 mcg/day (reference range, < 40 mcg/day) in most patients with symptomatic Wilson disease, but it may also be elevated in other cholestatic liver diseases

· In a patient with Kayser-Fleischer rings, a serum ceruloplasmin level < 0 mg/dL and 24-hoyr urine copper excretion >40 mcg/day establish the diagnosis of Wilson disease

· Hepatic copper concentration (criterion standard) on a liver biopsy specimen is >250 mcg/g of dry weight even in asymptomatic patients; a normal result (15-55 mcg/g) effectively excludes the diagnosis of untreated Wilson disease, but elevation may be found in other chronic hepatic disorders

· Radiolabeled copper testing directly assays hepatic copper metabolism

· Genetic testing is limited to screening of family members for an identified mutation detected in the index patient

· Brain imaging shows characteristic findings; MRI appears to be more sensitive than CT in detecting early lesions

· Abdominal imaging findings are neither sensitive nor specific

· Resting ECG abnormalities include left ventricular or biventricular hypertrophy, early repolarization, ST segment depression, T-wave inversion, and various arrhythmias

· Electron microscopic detection of copper-containing hepatocytic lysosomes is helpful in the diagnosis of the early stages of Wilson disease, in addition to the quantification of hepatic copper by atomic absorption spectrophotometry¹¹

EXAMS AND TESTS

A slit-lamp eye examination may show:

· Limited eye movement

· Rusty or brown-colored ring around the iris (Kayser-Fleischer rings)¹¹

A physical examination may show signs of:

· Damage to the central nervous system, including loss of coordination, loss of muscle control, muscle tremors, loss of thinking and IQ, loss of memory, and confusion (delirium or dementia)

· Liver or spleen disorders (including cirrhosis, splenomegaly, and liver necrosis)¹¹

Lab tests may include:

· Complete blood count (CBC)

· Serum ceruloplasmin

· Serum copper

· Serum uric acid

· Urine copper¹¹

If there are liver problems, lab tests may find:

· High AST and ALT

· High bilirubin

· High PT and PTT

· Low albumin¹¹

Other tests may include:

· 24-hour urine copper test

· Abdominal x-ray

· Abdominal MRI

· CT scan of the abdomen

· Head CT scan

· Head MRI

· Liver biopsy

The gene that causes Wilson disease has been found. It is called ATP7B. DNA testing is available for this gene. Talk to your health care provider or a genetic counselor if you would like to have gene testing performed.¹¹

TREATMENT

Drug Management

The goal of treatment is to reduce the amount of copper in the tissues. This is done by a procedure called chelation -- certain medications can bind to copper and help remove it through the kidneys or gut. Treatment must be lifelong.

The following medications may be used:

· Penicillamine (Cuprimine, Depen) binds to copper and leads to increased release of copper in the urine.

· Trientine (Syprine) binds (chelates) the copper and increases its release through the urine.

· Zinc acetate (Galzin) blocks copper from being absorbed in the intestinal tract.

· Vitamin E supplements may also be used.

Sometimes, medications that chelate copper (especially penicillamine) can affect the function of the brain and nervous system (neurological function). Other medications under investigation may bind copper without affecting neurological function.¹¹

Other drugs for Wilson disease include the following:

· Anticholinergics, baclofen, GABA antagonists, and levodopa to treat dystonia

· Antiepileptics to treat seizures

· Neuroleptics to treat psychiatric symptoms

· Protein restriction, lactulose, or both to treat hepatic encephalopathy

Diet Management

A low-copper diet may also be recommended. Foods to avoid include:

· Chocolate

· Dried fruit

· Liver

· Mushrooms

· Nuts

· Shellfish

· You may want to drink distilled water because most tap water flows through copper pipes. Avoid using copper cooking utensils.

· Symptoms may be treated with exercise or physical therapy. People who are confused or unable to care for themselves may need special protective measures.¹¹

Surgical Management

· Surgical decompression or trans jugular intra hepatic shunting (TIPS) is reserved for recurrent or uncontrolled variceal bleeding unresponsive to standard conservative measures

· A liver transplant may be considered in cases where the liver is severely damaged by the disease.¹¹

COMPLICATIONS

People who have Wilson disease that is not treated or diagnosed early can have serious complications, such as

· Cirrhosis—Scarring Of The Liver

· Kidney Damage—As Liver Function Decreases, The Kidneys May Be Damaged

· Persistent Nervous System Problems When Nervous System Symptoms Do Not Resolve

· Liver Cancer—Hepato cellular Carcinoma Is A Type Of Liver Cancer That Can Occur In People With Cirrhosis

· Liver Failure—A Condition In Which The Liver Stops Working Properly

· Death, If Left Untreated¹²

PREVENTION

· A person cannot prevent Wilson disease; however, people with a family history of Wilson disease, especially those with an affected sibling or parent, should talk with a health care provider about testing.

· A health care provider may be able to diagnose Wilson disease before symptoms appear.

· Early diagnosis and treatment of Wilson disease can reduce or even prevent organ damage.

· People with a family history of the disease may also benefit from genetic testing that can identify one or more gene mutations.

· A health care provider may refer a person with a family history of Wilson disease to a geneticist—a doctor who specializes in genetic diseases.¹²

NURSING MANAGEMENT:

· The identity of the child: name, age, address, education level, etc..

· Past medical history: previous ever hurt a child like this?

· Birth history, growth, disease that is often experienced by children, immunizations, previous hospitalization, and medication allergies.

· The pattern of daily habits: eating and drinking, hygiene patterns, the pattern of bed rest, activity or play, and elimination patterns.

· General Assessment: vital signs, weight, height, head circumference, chest circumference¹²

CONCLUSION:

Wilson disease is a genetic disease that prevents the body from removing extra copper. Normally, the liver filters extra copper and releases it into bile. In Wilson disease, the liver does not filter copper correctly and copper builds up in the liver, brain, eyes, and other organs. Wilson disease is caused by an inherited autosomal recessive mutation, or change, in the ATP7B gene. In an autosomal recessive disease, the child has to inherit the gene mutation from both parents to have an increased likelihood for the disease. A person cannot prevent Wilson disease; however, people with a family history of Wilson disease, especially those with an affected sibling or parent, should talk with a health care provider about testing.

REFERENCES:

1. Food and Nutrition Board: Recommended Dietary Allowances, 9th Ed. National Academy of Sciences, Washington, D.C., 1980.

2. Li, T-K. and Vallee, B. L.: In Modern Nutrition in Health and Disease, 6th Ed. (R. S. Goodhart and M. E. Shils, Eds.). Philadelphia, Lea and Febiger, 1980, pp. 408-441.

3. Underwood, E. J.; Trace Elements, in Toxicants Occurring Naturally in Foods, 2nd Ed. Washington, D.C., Food and Nutrition Board, National Academy of Sciences, 1973, pp. 43-87.

4. http://www.chp.edu/CHP/wilsons+disease

5. https://en.wikipedia.org/wiki/Wilson%27s_disease

6. http://www.wilsonsdisease.org/about-wilsondisease.php

7. http://www.chp.edu/CHP/wilsons+disease

8. http://www.mayoclinic.org/diseases-conditions/wilsons-disease/ basics/causes/con-20043499

9. http://www.mayoclinic.org/autosomal-recessive-inheritance-pattern/img-20007457

10. http://emedicine.medscape.com/article/183456-overview

11. https://www.nlm.nih.gov/medlineplus/ency/article/000785.htm

12. http://www.niddk.nih.gov/health-information/health-topics/ digestive-diseases/wilson-disease/Pages/facts.aspx

Received on 05.11.2015 Modified on 29.10.2016

Asian J. Nur. Edu. and Research.2016; 6(4): 533-537.

DOI: 10.5958/2349-2996.2016.00099.9