Wilson's Disease

Basics

Wilson's disease is a familial, chronic and life-threatening copper metabolism disorder that requires urgent medical evaluation and treatment.

• In 1912, the British neurologist Samuel Wilson described the disease for the first time.
• Among other things, a gene defect inthe copper transport proteinATPase (ATP7B) is known as the decisive cause, whereby more than 700 mutations have been described in the meantime.
• Some mutations can lead to impaired biliary copper excretion, with toxic copper accumulation affecting the liver and brain in particular.- The disease is inherited in an autosomal recessive manner & is fatal in many cases if untreated.
• It is considered a rare disease because it occurs with a frequency of about 1:30,000.

What physiological role does copper play in the body?
Copper is essential as a trace element because it is involved in essential metabolic processes in various organs and tissues.

The percentage distribution of copper in individual organs and tissues of the human body is estimated as follows:

Examples of endogenous processes in which copper plays a role:

• Growth
• Angiogenesis & iron transport
• Immune defense system
• Bone & connective tissue strength
• Brain development
• Glucose metabolism
• Pigmentation of the skin, hair and eyes

How much copper does the human body need?

Under normal circumstances, the amount of copper is highly regulated, as non-protein-bound copper reacts toxically in the body and leads to severe organ damage at high concentrations. Therefore, the German Nutrition Society recommends the following estimated values for an adequate daily intake:

For example, 1 mg copper is contained in:

Symptoms

Although it is primarily the liver and brain that are restricted in their function, other organs can also be affected. According to epidemiological studies, the first symptoms appear between the ages of five and 45, and rarely thereafter.

Symptoms include:

Hepatic: chronic. hepatitis, liver cirrhosis and even liver failure. Symptoms usually appear from the age of 2.

Neurological: motor and coordination disorders can occur occasionally, such as tremor, movement disorders, but also writing, swallowing and speech disorders. Symptoms usually appear from the age of 15.

Psychiatric: psychiatric changes such as concentration disorders, mood swings or depression appear in about one third of those affected. Symptoms usually appear from the age of 15.

Ophthalmological: about 80% of patients show so-called Kayser-Fleischer rings, which stand out due to a 1-3 mm wide greenish-brown, reddish or golden-brown ring at the edge of the cornea. The rings are caused by copper deposition and do not have to be completely closed. The symptoms usually appear from the age of 10.

Course of the disease

The course of Wilson's disease sometimes varies greatly from patient to patient. This depends, among others, on the following factors:

• Type and severity of the mutations
• Sex
• Age, onset and severity of symptoms
• Time of diagnosis and start of therapy
• Adherence to therapy
• Comorbidities

If the diagnosis is made relatively early, i.e. in the still asymptomatic stage, and if therapy is initiated early and maintained throughout life, those affected have a fundamentally positive prognosis with regard to their life expectancy.

Diagnosis

The presumption of Wilson's disease usually follows:

• a family screening
• a suspected diagnosis based on symptoms typical of the disease
• any unexplained movement disorder
• a non-infectious liver symptomatology

The diagnosis is then usually confirmed by a number of tests. The following measures, among others, are taken to clarify the findings:

• Family history: Family screening of a diagnosed Wilson patient is necessary and involves all siblings (risk approx. 25 %) and children (risk approx. 0.5 %).
• Biochemical diagnostics: Urine copper excretion in 24h collection urine, blood count: including coagulation, liver enzymes, copper & -caeruloplasmin in plasma, kidney values.
• Histological examination: Copper determination via liver biopsy or puncture.
• Genetic diagnostics: A mutation analysis of the ATP7B gene can reveal disease-causing mutations in up to 98% of cases.
• Imaging techniques: CT, PET, MRI head, upper abdominal sonography.
• Electrophysiological diagnostics: EEG.

Therapy & Prevention

Although there is currently no cure for Wilson's disease, several oral medications are available that:

• prevent the onset of symptoms
• counteract the progression of the disease
• sometimes allow partial reversibility

Drug therapy is basically divided into two mechanisms of action:

Furthermore, in addition to a mandatory lifelong medication, a low-copper diet is advantageous. Supplementation with antioxidants such as vitamin E could also support the therapy of Wilson's disease.

In severe cases with a fulminant course, a liver transplant may be necessary for survival.

General notice:

The information on this website is for general educational purposes only and is not intended to make a diagnosis or to recommend a treatment. Please consult a doctor for any medical questions regarding this condition.

1. Biliary means "bilious", "pertaining to the gall bladder" or "belonging to the gall bladder".
2. Hepatic means "pertaining to the liver (hepar)".
3. Tremor: Tremor is a movement disorder with involuntary, strictly rhythmic and repetitive contractions of various muscle groups.
4. Cornea: the cornea is the foremost, strongly curved and transparent section of the eyeball that lies in front of the pupil.
5. Caeruloplasmin: Coeruloplasmin, CP for short, is a glycoprotein with binding and transport function for copper