A look into the complex world of genetic disorders, their histories, and how we treat them.
By Ian MacArthur
Each day, the human body’s wondrous capacity for regulation enables us to carry out our necessary tasks in the midst of an ever changing environment. Our ability to endure climates both scorching and frigid testifies to the body’s great control over its internal state, a quality termed homeostasis. Cellular processes are adapted to maintain the homeostatic balance required for the body to function in a vast range of environments. Although external conditions may vary a great deal without causing a human being much harm, even the slightest change in the body’s internal state can be catastrophic. Such is the case for the human regulation of copper, a micronutrient which in excess of a few milligrams per day can do great internal damage.
While the body’s homeostatic balance of copper is maintained through the concerted effort of a variety of proteins, patients of Wilson’s Disease are denied this crucial regulation. First diagnosed by Samuel Wilson in 1912, Wilson’s Disease is a genetic disorder characterized by the buildup of copper in the body’s tissues, primarily of the liver and brain. The ultimate consequences of this excess include liver failure, dementia, schizophrenia, and other grave ailments.
Mutations in the ATP7B gene located on chromosome 13 are the underlying cause of defective copper metabolism. The ATP7B protein which the gene codes for contains six copper binding sites, making it a key player in the elimination of copper from liver tissues. The defective protein in patients of Wilson’s Disease is unable to transfer cellular copper to the Golgi apparatus where it is prepared to be excreted by the cell. The result is the inability of the liver to eliminate copper and the metal’s consequent cellular buildup.
|A Kayser-Fleischer ring is a brown ring around the iris caused
by copper deposition in the eye. It is one of the most telling
signs of Wilson’s Disease. (image via Wikimedia Commons)
Patients may suffer from a variety of neurological, psychiatric, motor, and other symptoms. Dementia, insomnia, and seizures may result, as well as depression and schizophrenia. Muscle spasms can occur, and patients may have difficulty walking. One of the most distinct signs of Wilson’s is the presence of a brown ring around the iris, a feature called a Kayser-Fleischer ring, which is the result of copper deposition in the eye. The most serious symptoms of Wilson’s are hepatic in nature and include cirrhosis of the liver that can result in fatal failure of the organ.
Wilson’s Disease is an exceedingly rare illness, with a global prevalence of only 30 cases per million people. In order to inherit the disease, two mutated genes must be received by an individual from their parents, making Wilson’s a recessively inherited genetic disorder. A carrier of Wilson’s with only one defective copy of the ATP7B gene will not develop the disorder but has a 50% chance of passing the gene onto their child. A second copy must be received from the child’s other parent in order to develop symptoms.
Although patients with Wilsons’s are unable to biologically regulate their copper levels, the illness can be effectively treated by medicinal copper regulation. Drugs such as penicillamine and trientine are able to bind to copper through a process termed chelation and help eliminate it through urine. If taken throughout a patient’s life, these drugs can help to completely suppress disease symptoms. Such is the wonder of human homeostatic potential, that when our bodies fail to cope with a problem, our minds devise an effective solution.