Learn About Wilson’s Disease and How to Fight It
Wilson’s disease (WD) is a genetic disorder caused by mutations in the ATP7B gene. Mutations in this gene cause copper accumulation in the liver, brain, eyes, kidneys, bones, muscles, pancreas, lungs, and skin. The buildup of copper in the body occurs due to defects in the gene responsible for transporting copper out of cells. The defective gene prevents the protein coded by the gene from functioning properly. As a result, copper builds up in various organs of the body, including the liver, pancreas, kidneys, muscles, and bones. Symptoms of Wilson’s disease may appear at any age, but they tend to become noticeable between ages 2-10 years old. Wilson’s Disease affects about 1 in 30,000 people worldwide. WD affects copper transport across cellular membranes, resulting in excessive accumulation of copper in the liver, brain, kidneys, cornea, skin, muscles, and bone marrow. There are three types of Wilson’s Disease:
- Hepatic Wilson’s Disease – occurs when copper accumulates primarily in the liver
- Neurological Wilson’s Disease – occurs when copper accumulates mainly in the nervous system
- Mixed Wilson’s Disease– occurs when both hepatic and neurological manifestations occur
Wilson’s disease is characterized by abnormal accumulation of copper inside cells. Copper accumulates in the brain, liver, pancreas, kidneys, eyes, and muscles. People who have Wilson’s disease often experience symptoms related to these organs, including loss of coordination, tremors, memory lapses, muscle weakness, vision changes, seizures, hearing loss, depression, fatigue, and behavioral changes.
Diagnosis
Diagnosing WD is difficult due to its rarity. A definitive diagnosis requires a combination of clinical findings, laboratory tests, imaging studies, and genetic testing. Clinical features of WD include hepatomegaly, splenomegaly, jaundice, abnormal neurologic examination, and ocular abnormalities. Laboratory tests include elevated serum ceruloplasmin levels, low 24-hour urinary copper excretion, high hepatic copper concentration, and increased copper content in hair. Imaging studies include magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and nuclear medicine scans. Genetic testing includes DNA sequencing, mutation analysis, and Western blotting.
Symptoms
People with Wilson’s disease may experience symptoms, depending on where copper accumulates in the body. In its initial stage, Wilson’s disease often goes unnoticed. People may not notice any symptoms until later in adulthood. Common symptoms include fatigue, weakness, abdominal pain, diarrhea, nausea, vomiting, weight loss, headaches, depression, hearing problems, vision changes, joint pain, sexual dysfunction, and skin rashes.
Treatment
There is currently no known cure for Wilson’s disease. Treatment focuses on controlling symptoms and preventing complications. Medications that help control symptoms include zinc supplements, vitamin B12 injections, and NAC (N-acetyl cysteine). Zinc supplementation helps reduce the amount of copper in people’s blood. Vitamin B12 injections improve nerve function and help reduce the frequency of seizures. NAC reduces inflammation and increases the excretion of copper from the body. Surgery may also be considered to treat severe cases of Wilson’s.
In pregnancy, WD presents differently than in nonpregnant women. Women with WD have higher rates of miscarriage, stillbirth, preterm birth, low birth weight infants, and neonatal death. Pregnancy complications associated with WD include preeclampsia/eclampsia, placental abruption, intrauterine growth restriction, spontaneous abortion, fetal demise, and maternal death. The American College of Obstetricians and Gynecologists recommends that all pregnant women receive routine prenatal care, including screening for WD. If a woman tests positive for WD, she should be referred to a specialist for further evaluation and management.
Prevention
Early detection can prevent serious consequences. Early detection includes regular screening for symptoms of Wilson’s and monitoring the amount of copper in a person’s blood. Regular testing should begin between ages 10 and 20 years old.
Complications
The incidence of Wilson’s Disease (WD) varies worldwide. In the United States, approximately 1 in 30,000 people have WD. However, studies suggest that the prevalence rate may be much higher. Worldwide, there are about 50,000 cases per year.
In the early stage of WD, patients do not exhibit any clinical symptoms. As copper accumulates in the body, symptoms become apparent. Patients who develop symptoms may experience muscle weakness, joint pain, irritability, loss of appetite, weight loss, fatigue, headache, depression, anxiety, memory impairment, psychosis, tinnitus, dizziness, sleep disorders, vision changes, tremor, and paralysis.
There are two types of WD, type A and B. Type A can occur at birth or after childhood onset. In contrast, type B occurs later in adulthood and has a slower progression. Both forms of WD show similar symptoms. However, the age of onset differs between the two types.
- Type A is caused by mutations in the ATP7B gene located on chromosome 13q14.3-q21.1. The mutation causes decreased activity of Cu/Zn superoxide dismutase (SOD), leading to excess intracellular copper deposition and subsequent damage to the central nervous system.
- Type B is associated with mutations in the ceruloplasmin (CP) gene located on chromosome 12p13.1. CP transports copper ions out of cells. Mutations in the CP gene lead to reduced expression or abnormal function of CP, resulting in increased levels of free iron and copper. Free iron and copper accumulate in different parts of the body. Iron is deposited in various organs including the liver, heart, pancreas, muscles, and pituitary gland. Copper is mainly deposited in the basal ganglia region of the brain and the retina of the eye.
Despite extensive research, there has been little progress in developing effective treatments for Wilson’s Disease. Currently, only three FDA-approved drugs exist for treating Wilson’s Disease: zinc sulfate, trientine, and D-penicillamine. Zinc sulfate is the first choice drug. It works by decreasing intestinal absorption of copper, thereby lowering blood copper levels. Trientine is a second-line drug that works similarly to zinc but does not affect the gastrointestinal absorption of copper. D-penicillamine is the third-line drug and is a slow-acting inhibitor of the SOD enzyme.
Foods to Avoid
There are certain foods that people who suffer from Wilson’s Disease should not eat. These foods include wheat products, whole milk, legumes, and nuts. However, some foods like fresh fruit can help improve liver function and increase your liver enzymes. In addition, certain fruits like apples can reduce inflammation in the body and prevent cirrhosis. You may even want to consider eliminating alcohol because it can affect how well your liver works.
Tests Recommended
- Serum Copper Level Test: Wilson’s disease is happened by mutations in the ATP7B gene. Mutations in this gene result in insufficient copper excretion from the body. When blood levels of copper rise above standard limits, they may indicate that the patient has Wilson’s disease.
- 24-Hour Urinary Excretion Test: This test measures how much copper gets out from the urine over time. If there is not enough copper elimination, then this could mean that the person has Wilson’s disease. However, this test does not always detect Wilson’s condition if the copper level is below 25 mcg/24 hours. Also, patients who have been taking zinc supplements before the test might confuse copper results with those of Wilson’s disease.
- Liver Biopsy: The liver biopsy involves removing a small piece of liver tissue (about 1 cm^3) from the patient. A pathologist looks at the sample under a microscope to determine whether there is any evidence of Wilson’s disease present.
- Genetic Testing: Genetic testing is for people who have family members that have Wilson’s disease. If both parents carry the mutation, their children have a 50% chance of inheriting the condition.
Clinical Trials
The clinical trial is one of the most rigorous tests on humans. A clinical trial involves human subjects, where researchers take advantage of scientific methodology to examine the effects of treatments on people while they are under observation. To participate in a clinical trial, volunteers must first sign an informed consent document before any procedures begin. Clinical trials can last anywhere from several weeks to years.
Clinical Trials allow scientists to study drugs, medical devices, and treatments to determine their safety and effectiveness. Researchers use a variety of different methods to evaluate the performance of these products including interviews, questionnaires, lab testing (both physical and mental), imaging scans (such as x-rays), electrocardiograms (ECGs), body monitoring systems, blood draws, urine samples, and others.
