Wilson disease is a rare inherited disorder characterized by the accumulation of copper in various organs, particularly the liver and brain. It is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene (ATP7B) — one from each parent — to develop the condition. The ATP7B gene provides instructions for producing a protein involved in the transport of copper within the body. Wilson's disease is an autosomal recessive disorder that affects one in 100.000 people.
Wilson disease genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
The key features and aspects of Wilson's disease include:
- Copper Metabolism: Wilson disease results from a defect in the ATP7B gene, leading to impaired copper transport. Usually, copper is absorbed from the diet, processed in the liver, and excreted into bile for elimination. In individuals with Wilson disease, copper accumulates in the liver and cannot be excreted appropriately, leading to toxicity.
- Hepatic Manifestations: Hepatic symptoms are common in Wilson's disease. These may include hepatomegaly (enlarged liver), jaundice (yellowing of the skin and eyes), and liver dysfunction. In severe cases, it can lead to liver failure.
- Neurological Manifestations: Copper buildup in the brain can result in neurological symptoms. These may include movement disorders such as tremors, rigidity, and difficulty with coordination. Psychiatric symptoms, such as mood swings, depression, and cognitive impairment, can also occur.
- Kayser-Fleischer Rings: A characteristic sign of Wilson disease is the presence of Kayser-Fleischer rings, which are copper deposits in the cornea of the eyes. These rings appear as a golden-brown discoloration encircling the iris and are visible during an eye examination.
- Renal Involvement: Copper can accumulate in the kidneys, leading to renal dysfunction.
- Diagnostic Tests: Diagnosis of Wilson disease involves a combination of clinical evaluation, liver function tests, measurement of copper levels in the blood and urine, genetic testing to identify mutations in the ATP7B gene, and the presence of Kayser-Fleischer rings.
- Treatment: Wilson's disease is treatable, and management aims to reduce copper levels in the body. The primary treatment is copper-chelating medications, such as penicillamine and trientine, which help remove excess copper from the body. Zinc supplements may also inhibit copper absorption in the digestive tract. In severe cases or cases of liver failure, liver transplantation may be considered.
- Lifelong Management: Wilson's disease requires lifelong management to control copper levels and prevent the progression of symptoms. Regularly monitoring copper levels, liver function, and neurological status is essential.
Early detection and intervention are crucial for managing Wilson's disease effectively. Treatment initiated in the early stages of the disease can help prevent irreversible organ damage. Regular follow-up with healthcare professionals, including hepatologists and neurologists, is essential for ongoing care and adjustments to the treatment plan.
More Information
More than 500 pathogenic variants have been described that affect the ATP7B gene and give rise to Wilson's disease. Among these, c.3207C>A is the most common, affecting the ATP7B-ATP transporter binding domain. The allele frequency of c.3207C>A in the Eastern European, German, French, and British populations is 28%. It is expected to find patients presenting c.3207C>A in heterozygosis with the c.2293G>A variant.
The c.3796G>A mutation also affects the ATP-binding protein domain, reducing the protein's transporting capacity. Its allelic frequency is 10% in the British and French populations and can be found in compound heterozygosis. The c.3809A>G variant also causes defects in copper transport and has been found in homozygosity and compound heterozygosity with other pathogenic variants.
Various variants affect the protein's transmembrane domain as c.1934T>G and c.2123T>C. The variant c.2123T>C represents 50% of the pathogenic alleles identified in the Canary Islands.
They have also been described as variants that produce a truncated form of the transporter, such as c.865C>T, which is associated with the severe form of the disease, and mutations that significantly affect the structure of the protein and its function, such as c.2071G>A.
Wilson disease genetic testing analyzes the 80 most frequent pathogenic mutations of the ATP7B gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
