Wilson Disease Genetic Tests

Wilson Disease Genetic TestsClinical Features in Patients with Wilson DiseaseHepatic well hepatomegalyIsolated splenomegalyPersistently elevated serum aminotransferase activity (AST, ALT)Fatty colored, Acute hepatitis, Resembling autoimmune hepatitisCirrhosis compensated or decompensatedAcute coloured failureNeurologicalMovement disorders (tremor, involuntary movements)Drooling, dysarthria, Rigid dystoniaPseudobulbar palsy, Dysautonomia, Migraine headaches, Insomnia, SeizuresPsychiatricDepression, Neurotic behaviours, Personality changes, Psychosis otherwise SystemsOcular Kayser-Fleischer rings, sunflower cataractsCutaneous lunulae ceruleae Renal abnormalities aminoaciduria and nephrolithiasisSkeletal abnormalities premature osteoporosis and arthritis Cardiomyopathy, dysrhythmias Pancreatitis HypoparathyroidismMenstrual irregularities infertility, repeated miscarriagesHow is Wilson unsoundness diagnosed?The diagnosis of Wilson ailment is made by relatively simple assays. Th e tests layabout diagnose the disease in both symptomatic patients and people who show no signs of the disease. These tests endure includeOpthalmalogic slit lamp psychometric test for Kayser-Fleischer ringsSerum ceruloplasmin test24-hour urine slob testLiver biopsy for histology and histochemistry and copper quantificationGenetic examination, haplotype analysis for siblings and mutation analysis.It is important to diagnose Wilson disease as early as possible, since severe liver damage can occur before there are any signs of the disease. Individuals with Wilson disease may falsely appear to be in excellent health.Treatment of Wilson diseaseWilson disease is a very treatable condition. With proper therapy, disease progress can be halted and oftentimes symptoms can be improved. Treatment is aimed at removing lavishness accumulated copper and preventing its reaccumulation. Treatment for Wilson disease is a lifelong process. Patients may become progressively sicker from day to day, so immediate treatment can be critical. Treatment delays may cause irreversible damage.Chelation therapy drugs approved for treating Wilson disease include penicillamine (Cuprimine and Depen) and trientine (Syprine and Trientine Dihydrochloride) Both of these drugs act by chelation or binding of copper, causing its increased urinary excretion.Mettalothi hotshotin inducer drugs approved for treating Wilson disease are (Galzin) in the U.S. and (Wilzin)in Europe.Zinc acts by blocking the absorption of copper in the intestinal tract. This action both depletes accumulated copper and prevents its reaccumulation. Zincs strength has been shown by more than 30 years of considerable experience all overseas. A major advantage of zinc therapy is its lack of side effects.Patients with severe hepatitis or liver failure may require liver transplant. Patients being investigated or treated for Wilson disease should be cared for by specialists in Wilson disease or by specialists in consultation w ith their primary physicians. Stopping treatment completely will result in death, sometimes as quickly as within three months. diminish dosage of medications also can result in unnecessary disease progression.How is Wilson disease inherited?Wilson disease is an autosomal recessive disease, which means it occurs equally in men and women. In order to inherit Wilson disease, both parents must carry unrivaled componenttic mutation (abnormal alteration in the gene) that each parent passes to the bear upon child. At least one in 30,000 people of all cognise races and nationalities has the disease. Of the 23 different human chromosomes, the gene responsible for Wilson disease is located on chromosome 13. The gene is called ATP7B and it contains the genetic information necessary to make a copper transport protein that plays a key role in incorporating copper into ceruloplasmin and moving excess copper out of the liver. Mutations in the gene lead to an abnormal copper transporter that c annot move copper effectively or at all. More than ccc genes of the ATB7B have been identified thus far.This excess copper accumulates in the liver and other organs. Most patients have no family history of Wilson disease. People with only one abnormal gene are called carriers. Carriers (heterozygotes) may have mild, but medically insignificant, abnormalities of copper metabolism. Carriers do not become ill and should not be treated. Wilson disease patients (homozygotes) do become ill and must receive treatment lifelong or eventually they will develop severe lethal disease.One in 100 individuals in the general population carries one abnormal copy of the Wilson disease gene. Carriers have one normal and one abnormal gene. wholly (100%) children of those impaired with Wilson disease receive at least one abnormal copy of the Wilson disease gene. One half (50%) of a carriers children receive at least one abnormal copy of the Wilson disease gene. A genetic counselor can provide a more d etailed pedigree of specific family relationships.Family ScreeningAll siblings and children of Wilson disease patients should be well-tried for Wilson disease. Other relatives who have had symptoms or laboratory tests that indicate liver or neurological disease also should be tested for Wilson disease. Biochemical Testing Children of patient Begin at age 2 if asymptomatic, repeat once in 5 years unless reasontopursue further.Siblings of patientPhysical examination and brief history of any liver or neurological symptoms.Liver Function Tests ALT, AST, Albumin, Bilirubin.Ceruloplasmin and Serum Copper.24 hour urine copperSlit-lamp exam of the eyeball for Kayser-Fleischer rings.If no K-F rings, abnormal liver functions tests, and low ceruloplasmin liver bioInformation about Molecular Genetic TestingAll siblings and children of Wilson disease patients should be tested for Wilson disease. Other relatives who have had symptoms or laboratory tests that indicate liver or neurological disea se also should be tested for Wilson disease. More than 300 different mutations of the ATP7B gene have been identified thus far.Testing Methods AvailableLinkage analysis (Haplotype analysis) Molecular genetic test to identify a set of closely link segments of DNA (a marker or set of markers), comparing the markers of family members to those of an affected patient.Useful for screening siblings of an identified patient Gene sequencing (mutation screening of the wide ATP7B gene) Analysis of the entire ATP7B gene to detect and identify disease causing mutations. An individual with confirmed Wilson disease needs to be tested first. If both mutations are identified, other family members can then be offered testing. Gene sequencing will identify both mutations in most but not all cases of Wilson disease.Useful for confirmation of the diagnosis in suspected patients, family members to learn if they could be affected but do not yet have symptoms, to learn they are carriers, or to allow for prenatal testing for confirmed carriers.Analysis of a specific location in the ATP7B gene for a known particular mutation.Useful for specific populations of patients where the common mutations are known for screening siblings of patients with two identified mutations. Genetic testing is ruff coordinated through a genetic counselor who can carefully debate the best method of testing to perform and the benefits, limitations, and implications of each method. Genetic testing is best coordinated though a genetic counselor who can carefully discuss the best method of testing to perform and the benefits, limitations, and implications of each method. Your physician should be able to direct you to a qualified genetic counselor and genetic testing facility.Definition Kayser-Fleischer Ring Clinical sign. Brownish-yellow ring visible around the corneo-scleral junction (limbus). Consists of copper deposits in Descemets membrane, extending into the trabecular meshwork. Sign of Wilsons disease. comment and Location Golden to greenish-brown annular deposition of copper located in the periphery (limbus) of the cornea (Descemets membrane). First appears as a superior crescent, then develops inferiorly and finally becomes circumferential. Usually requires a slit-lamp examination to detect rings in their early stage of formation.Prevalence Approximately 95% of WD patients presenting with neurological signs will have a K-F ring. Whereas approximately 65% of WD patients presenting with hepatic signs will present with a ring.Copper chelation therapy may cause fading and even disappearance of the corneal copper over time.