Diana s Genetics -Review Paper Wilson's Disease Occurs in approximately 1 in 30,000 individuals, Wilson s disease is a relatively are disorder known for the over accumulation of copper in tissues. This copper metabolism disease is an autosomal recessive genetic disorder, meaning a patient must inherit a copy of mutated gene from both parent in order to be clinically symptomatic. The over accumulation of copper in the body often manifest as neurological or psychiatric symptoms, and liver disease. This is because the main site of copper accumulation is usually the liver and brain the gene responsible for the Wilson's disease would be the atp7B gene, located on the 13th chromosome Signs and symptoms Since the main site of copper accumulation is the brain and liver europsychiatric symptoms and liver disease are usually the main features that lead to diagnosis. Patients that develop liver disease usually present symptoms such as tiredness, fatigue, jaundice, loss of appetite, and abdominal swelling However, symptoms of liver disease can be considerably subtle at times and could be often ignored. Thus, about 5% patients do not realize the disease until an acute liver failure On the other hand accumulation of copper in the brain will lead to neurological and psychiatric presentations. Neurological symptoms may include tremors, poor coordination, and cognitive disorders, such as poor memory, judgment, and reasoning. While, psychiatric disturbances include depression, neurotic behaviors, disorganization in personality and intellectual deterioration although brain and liver is the common site for copper accumulation, some patients can also have copper accumulation in the eye, resulting in Kayser- Fleischer rings. the KF rings rarely impair vision, but is a obvious sign that leads to diagnosis Clinical Diagnosis Often times, the initial steps for clinical diagnosis of Wilson s disease are test for a)low ceruloplasmin concentration, b) high urinary copper c)increased hepatic copper concentration. If a patient tests positive for 2 out of the 3 above then it is a strong support for the Wilson s disease diagnosis. However, in order to 100% confirm if a person has Wilson s disease, it is ideal to perform a molecular genetic testing given that the disease is a genetic disorder. Related Gene The main gene involved in the wilson s disease is the atp7b gene mapped on the 13th chromosome(13q14.3-q21 1). the mutation on this gene would cause Wilsons disease. The atP7b gene provides instruction for making protein responsible for copper transport and elimination When this gene is damaged and cannot perform responsible tasks, copper accumulation will lead to tissue and organ Another gene related, but not involved in Wilson's disease would be the PRNp
Diana Tseng Genetics – Review Paper Dr. Liu Wilson’s Disease Occurs in approximately 1 in 30,000 individuals, Wilson’s disease is a relatively rare disorder known for the over accumulation of copper in tissues. This copper metabolism disease is an autosomal recessive genetic disorder, meaning a patient must inherit a copy of mutated gene from both parent in order to be clinically symptomatic. The over accumulation of copper in the body often manifest as neurological or psychiatric symptoms, and liver disease. This is because the main site of copper accumulation is usually the liver and brain. The gene responsible for the Wilson’s disease would be the ATP7B gene, located on the 13th chromosome. Signs and Symptoms Since the main site of copper accumulation is the brain and liver, neuropsychiatric symptoms and liver disease are usually the main features that lead to diagnosis. Patients that develop liver disease usually present symptoms such as tiredness, fatigue, jaundice, loss of appetite, and abdominal swelling. However, symptoms of liver disease can be considerably subtle at times and could be often ignored. Thus, about 5% patients do not realize the disease until an acute liver failure. On the other hand, accumulation of copper in the brain will lead to neurological and psychiatric presentations. Neurological symptoms may include tremors, poor coordination, and cognitive disorders, such as poor memory, judgment, and reasoning. While, psychiatric disturbances include depression, neurotic behaviors, disorganization in personality, and intellectual deterioration. Although brain and liver is the common site for copper accumulation, some patients can also have copper accumulation in the eye, resulting in Kayser- Fleischer rings. The KF rings rarely impair vision, but is a obvious sign that leads to diagnosis. Clinical Diagnosis Often times, the initial steps for clinical diagnosis of Wilson’s disease are test for: a) low ceruloplasmin concentration, b) high urinary copper, c) increased hepatic copper concentration. If a patient tests positive for 2 out of the 3 above, then it is a strong support for the Wilson’s disease diagnosis. However, in order to 100% confirm if a person has Wilson’s disease, it is ideal to perform a molecular genetic testing, given that the disease is a genetic disorder. Related Gene The main gene involved in the Wilson’s disease is the ATP7B gene, mapped on the 13th chromosome (13q14.3-q21.1). The mutation on this gene would cause Wilson’s disease. The ATP7B gene provides instruction for making protein responsible for copper transport and elimination. When this gene is damaged and cannot perform responsible tasks, copper accumulation will lead to tissue and organ damage. Another gene related, but not involved in Wilson’s disease would be the PRNP
Diana s Genetics -Review Paper gene. Since the onset age for wilson s disease is greatly ranged from 6-50, a variation on the prnp gene could delay the age of onset. the prnp gene provides instruction for making prion protein and a variation in position 129 would result in the production of methionine instead of valine. this difference could delay the age of onset for wilson 's disease Treatment Wilsons disease cannot be completely cured, therefore patients require a life-long treatment and management protocol. Some drugs such as Penicillamine and Trietine can aid copper removal from the body. these drugs are commonly known as chleators, meaning that they bind to copper and lead to copper excretion throu urine. However, penicillamine may have severe side effects such as fever, rash leucopenia, and in worse cases, it can also drastically worsen neurological symptoms With better effect and tolerance, trietine has been gradually replacing Penicillamine as the first line treatment for wilson 's disease Another way to manage the condition of wilsons disease is to prevent copper bsorption from a patient 's daily diet. other than avoiding high copper food such as liver, brain, chocolate, mushrooms, shellfish, and nuts, oral Zinc can also prevent copper absorption. Since Zinc is a metallothionein inducer, it interferes with coppe absorption from the Gl tract and it induces enterocyte metallothionein, which binds with copper and eliminates through fece ver transplant is usually the last resort for patients that have an acute liver failure due to wilson 's di sease Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders and to help them make informed medical and personal decisions. Since Wilson s disease is an autosomal recessive genetic disorder both parent has to pass down a copy of a mutated atP7B gene to their child in order for him or her to develop the disease Parents of a proband are obligated carriers or heterozygous, and also could be patients of Wilsons disease. Carriers usually are asymptomatic and do not develop any clinical disease. Siblings of a proband have a 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being unaffected and not a carrier. Offspring of a proband are obligated carriers but given that the carrier rate in the general population is about 1 in 90 the chance for the offspring to be affected is about 1 in 180 which is a considerably low probability although carriers are rarely of any clinical significance, carrier status should still be identified for future family planning considerations
Diana Tseng Genetics – Review Paper Dr. Liu gene. Since the onset age for Wilson’s disease is greatly ranged from 6-50, a variation on the PRNP gene could delay the age of onset. The PRNP gene provides instruction for making prion protein and a variation in position 129 would result in the production of methionine instead of valine. This difference could delay the age of onset for Wilson’s disease. Treatment Wilson’s disease cannot be completely cured, therefore patients require a life-long treatment and management protocol. Some drugs such as Penicillamine and Trietine can aid copper removal from the body. These drugs are commonly known as chleators, meaning that they bind to copper and lead to copper excretion through urine. However, penicillamine may have severe side effects such as fever, rash, leucopenia, and in worse cases, it can also drastically worsen neurological symptoms. With better effect and tolerance, Trietine has been gradually replacing Penicillamine as the first line treatment for Wilson’s disease. Another way to manage the condition of Wilson’s disease is to prevent copper absorption from a patient’s daily diet. Other than avoiding high copper food such as liver, brain, chocolate, mushrooms, shellfish, and nuts, oral Zinc can also prevent copper absorption. Since Zinc is a metallothionein inducer, it interferes with copper absorption from the GI tract and it induces enterocyte metallothionein, which binds with copper and eliminates through feces. Liver transplant is usually the last resort for patients that have an acute liver failure due to Wilson’s disease. Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders and to help them make informed medical and personal decisions. Since Wilson’s disease is an autosomal recessive genetic disorder, both parent has to pass down a copy of a mutated ATP7B gene to their child in order for him or her to develop the disease. Parents of a proband are obligated carriers or heterozygous, and also could be patients of Wilson’s disease. Carriers usually are asymptomatic and do not develop any clinical disease. Siblings of a proband have a 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being unaffected and not a carrier. Offspring of a proband are obligated carriers, but given that the carrier rate in the general population is about 1 in 90, the chance for the offspring to be affected is about 1 in 180, which is a considerably low probability. Although carriers are rarely of any clinical significance, carrier status should still be identified for future family planning considerations
