Willson disease

Wilson disease (also called hepatolenticular degeneration) is a rare inherited genetic disorder characterized by impaired copper metabolism, leading to excessive copper accumulation in organs and tissues, primarily the liver and brain, which causes the associated symptoms.

This disorder is inherited in an autosomal recessive manner, meaning a child with Wilson disease inherits defective genes from both parents, who are typically healthy carriers. Two defective genes—one from each parent—are required for the disease to manifest. If both parents are carriers, there is a 25% chance the child will have Wilson disease, a 50% chance the child will be a healthy carrier, and the risk is equal for both sexes.

Studies show that mutations in the ATP7B gene are responsible for Wilson disease. This gene plays a critical role in transporting and excreting copper via bile into the digestive tract. Over 300 mutations of the ATP7B gene have been identified that cause Wilson disease. The prevalence is approximately 1 in 30,000–40,000 people, and it occurs equally across all ethnic groups.

Signs and Symptoms:
One of the earliest signs of Wilson's disease is most often liver damage, which begins around the age of 6, but clinically manifests only in the teenage years or in the early twenties. Liver damage, up to liver failure, generally presents with yellowing of the whites of the eyes, yellowish skin tone, non-infectious jaundice, itching of the skin, swelling of the lower limbs, and even ascites (presence of free fluid in the abdominal cavity), esophageal varices (abnormally engorged veins in the esophagus with risk of rupture and bleeding), nausea, loss of appetite, excessive bleeding (due to poor blood clotting), and fatigue. Some patients with Wilson's disease may have liver failure as the only symptom of the disease for many years.

Only a few patients with Wilson's disease experience severe liver failure. It occurs more often in females and adolescents. Such liver failure may also be accompanied by anemia due to hemolysis (breakdown of red blood cells) and neurological difficulties such as disorientation. In almost all patients in this scenario, the typical Kayser-Fleischer ring is absent; this is a golden-brown coloration of the cornea due to copper deposition in the Descemet membrane of the cornea, more pronounced at the upper edge of the cornea.

If liver damage is not detected, neurological symptoms develop. These symptoms include tremor—involuntary muscle movements of the limbs—dysphagia (swallowing difficulties), speech and articulation disorders (dysarthria), poor coordination, spasticity, and muscle stiffness. Almost all patients with neurological symptoms also exhibit the typical Kayser-Fleischer ring.

Behavioral disorders present a wide range of manifestations. Symptoms may include disorientation, depressive states, and schizophrenia. These symptoms can be misdiagnosed, and the overall condition may be attributed to substance use. Personality disorders may also be present. These symptoms often occur alongside neurological signs, with the Kayser-Fleischer ring developing a few years later.

In women, insufficient liver function causes hormonal imbalance, resulting in irregular menstrual cycles, missed periods, or complete absence of menstruation in girls (amenorrhea), recurrent miscarriages, or infertility.

Kidney involvement manifests as the formation of kidney stones and damage to the renal tubules. Additionally, arthritis, osteoporosis, or other joint diseases may also be present.

Diagnosis:
Diagnosis is based on clinical signs, ultrasonographic and laboratory examinations (elevated liver enzymes in the blood), which indicate liver failure, as well as differential diagnosis to distinguish liver damage from other external causes (such as alcohol-related or viral damage) using laboratory tests. In Wilson's disease, there is typically a low concentration of ceruloplasmin (a protein that binds copper) and a high concentration of copper in the urine and blood. Often, a liver biopsy is required to confirm the diagnosis.

In cases of neurological and psychiatric symptoms, it is necessary to differentiate Wilson's disease from other neurological disorders (such as Parkinson’s disease), supplemented by magnetic resonance imaging, which typically shows characteristic involvement of the basal ganglia. Ophthalmologic examination is also important to confirm the presence of a Kayser-Fleischer ring.

Because the disease’s manifestations result from chronic copper accumulation in the body (chronic copper intoxication), the most commonly used treatment is reducing copper intake through diet and facilitating copper removal from the body—primarily using penicillamine and zinc preparations. Liver transplantation is a possible, though highly invasive, treatment option.

Genetic testing through DNA analysis is used to confirm the gene mutation, which usually confirms the mutation. It is also important to test siblings to determine whether they are carriers of the defective gene.

Treatment:
Early diagnosis and therapy are crucial to prevent further complications, halt organ damage—particularly to the brain and liver—and avoid irreversible organ injury.

Treatment of Wilson's disease is lifelong and focuses on reducing copper intake to prevent excessive copper accumulation in the body.

The first group of medications promotes copper excretion through urine (penicillamine). The second group consists of zinc salts, which reduce copper absorption from the digestive tract. The third group combines these two approaches—preventing copper absorption in the intestines and converting toxic copper in the blood into a non-toxic form.

Liver transplantation is a life-saving therapy for patients with advanced liver cirrhosis.

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