How copper damages organs
The body needs copper in small quantities: it is part of enzymes. From food, it is absorbed in the intestines and enters the liver, from where the excess is normally excreted with bile. In Wilson-Konovalov disease, the transporter protein responsible for this output and for the incorporation of copper into the ceruloplasmin protein is disrupted. Copper accumulates in liver cells, damaging them, causing inflammation and fibrosis. When the liver's capacity is exhausted, free copper enters the blood and settles in the basal ganglia of the brain, cornea, kidneys and joints.
- Hepatic form - hepatitis, cirrhosis, acute liver failure
- Neurological form - trembling, speech and gait disturbances
- Psychiatric form - changes in behavior and mood
- Mixed form, most common
- Asymptomatic stage detected during examination of relatives
Symptoms
Hepatic manifestations vary: from incidentally found increases in ALT and AST to severe jaundice. In some adolescents, the disease debuts as acute hepatitis with anemia due to the destruction of red blood cells. Neurological signs develop gradually: trembling of the hands, which increases with movement, slowness, stiffness, slurred speech, drooling, difficulty writing. Often, character and academic performance are the first to change: irritability, impulsiveness, decreased academic performance, and depression appear, which are mistakenly attributed to adolescence.
- Weakness, heaviness in the right hypochondrium, liver enlargement
- Jaundice, dark urine
- Trembling of hands, head, lack of coordination
- Slurred speech, difficulty swallowing
- Muscle stiffness, changes in handwriting
- Mood swings, irritability, depression
- Kayser-Fleischer rings along the edge of the cornea
Diagnostics
Age helps to suspect the disease: unexplained liver damage or new tremors in a person under 40 years of age require the exclusion of a copper metabolism disorder. Basic studies include blood ceruloplasmin, which is usually decreased, and 24-hour urinary copper excretion, which is increased. An important detail is an examination by an ophthalmologist with a slit lamp for Kayser-Fleischer rings: in the neurological form they are almost always present. For neurological complaints, an MRI of the brain is performed. The diagnosis is confirmed by genetic testing, and sometimes a liver biopsy is required.
- Serum ceruloplasmin
- Daily urinary copper excretion
- Free serum copper
- Liver tests, bilirubin, albumin, coagulogram
- Examination by an ophthalmologist with a slit lamp
- Ultrasound and elastography of the liver
- MRI of the brain
- Genetic and sibling testing
Treatment
The goal of therapy is to remove accumulated copper and prevent it from accumulating again. At the first stage, chelating drugs are used, which bind copper and remove it in the urine. After achieving stability, they switch to maintenance therapy: a lower dose of a chelator or zinc salt, which blocks the absorption of copper in the intestine. Treatment is lifelong: unauthorized withdrawal after months or years leads to the return of the disease, sometimes in the form of severe liver failure. All medications and doses are selected by the doctor; regular monitoring of tests is necessary.
- Copper chelators in the initial phase of treatment
- Zinc preparations for maintenance therapy
- Regular monitoring of urine copper, liver tests and general blood tests
- Diet with restriction of liver, shellfish, nuts, mushrooms, cocoa
- Avoiding alcohol and copper utensils
- Symptomatic help from a neurologist for tremors and stiffness
- Liver transplantation for acute liver failure and decompensated cirrhosis
Observation and forecast
When treatment is started before the development of cirrhosis and severe brain changes, the prognosis is good: liver function is restored, neurological symptoms largely go away, although improvement may take up to a year. It is important that in the first weeks of therapy, neurological complaints sometimes temporarily intensify - the doctor warns about this, and this is not a reason to quit treatment. The patient is monitored for life with control tests several times a year. All brothers and sisters must be examined, including those who have no complaints.
- Follow-up visits and tests every 6–12 months after stabilization
- Assessment of adherence to treatment is the main reason for deterioration
- Screening of first-degree blood relatives
- Planning pregnancy together with a doctor; therapy is not interrupted without permission
- Monitoring Liver Fibrosis
- Rehabilitation and classes with a speech therapist for neurological forms