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Wednesday, September 28, 2011

Metallic gene- a rare genetic mutation called Wilson's disease can make youngsters behave erratically

Metallic gene A rare genetic mutation, Wilson’s disease, caused 15-year-old Aditya Tiwari to behave erratically, which led to him being expelled from school. He’s now on the road to recovery Ankit Ajmera Posted On Thursday, September 29, 2011 at 04:15:25 AM Three years ago, late one night, 12-year-old Aditya Tiwari was kicked out of the house. His father Manoj Tiwari left him standing alone on a highway. Aditya had been watching TV the whole day. When his father switched it off, Aditya started hitting him. Aditya’s irresponsible, aggressive and errant behaviour had become a menace for the family. He had hit his mother, troubled his little sister, never did his homework, tore his books, masturbated frequently and quarrelled with friends. What Manoj didn’t know was that his son, now 15 years old, was suffering from a rare genetic disorder called Wilson’s disease that had changed him from a normal boy to an erratic aggressive child almost suddenly. The neurological and motor damage happened within a span of six months. What is Wilson’s disease? Dr Mohit Bhatt, consultant neurologist and movement disorder specialist at Kokilaben Dhirubhai Ambani Hospital, explains that Wilson’s disease is caused when a defective XX or XY gene is transferred from both the parents to the child. When two defective genes, one from each parent combine, it impacts the ceruloplasmin enzyme which is responsible for metabolising copper in the body. In healthy people, the liver excretes most of the unnecessary copper through the kidneys with the help of the ceruloplasmin enzyme. When the liver is unable to produce it, copper is released into the blood stream and travels throughout the body damaging the brain, kidneys, liver and eyes. The body starts showing symptoms of the disease between the age of 6 and 20. In most cases the disease goes undiagnosed because it doesn’t have a set pattern of symptoms. Some common variations are — changes in one’s personality, speech impairment, hyper-sexuality, repeated jaundice, difficulty in movement and uncontrolled aggression or depression. The onset Aditya was studying in Class Five when the disease hit him. His concentration in studies dipped and his grades dropped. “Every day there was a complaint from his school,” says his father, who works as a salesman. “He had failed in a class test, spoilt his book by salivating on it or picked up a fight with one of his classmates. Like us, the teachers too didn’t have clue what was going on with our son. The only thing he would do constantly is watch television and annoy his sister who is four years younger. He had become irritable and did not like anybody objecting to what he was doing,” says Manoj. Things got out of hand when Aditya bashed up one of his classmates and injured him. “He had stolen my book. I was just trying to get it back,” says Aditya. His speech at the time had deteriorated and he couldn’t explain himself. The school authorities found his behaviour unacceptable and rusticated him from the school. Manoj was shattered and decided to throw him out of the house. He later realised his mistake and after frantic hours of searching, Aditya was found across the highway at his uncle’s house. He was taken to the doctor and diagnosed with Wilson’s disease. It had manifested itself in the form of speech impairment, difficulty in walking, aggression and hyper sexuality. The way out The treatment involves a medication that traps the copper in the blood and releases it through urine. However, due to high doses of Penicillamine, a drug used in Wilson’s treatment, Aditya’s condition got worse. The side effects further slowed down his motor and cognitive functions. Dr Bhatt finally came to Manoj’s rescue and helped them with the right treatment. According to Bhatt, if the disease is not treated in time, symptoms such as hyper sexuality can become uncontrollable. “If hypersexual patients have the means, they would watch porn incessantly, visit prostitutes, masturbate regularly and even grab someone in public. However, Aditya’s case wasn’t as severe,” says Bhatt. Path to Recovery It’s been two years since Aditya started the treatment and life is almost back to normal. He has overcome his aggression and motor impairment. He still slurs while talking but his condition is improving. With time, the dosage of medicines will reduce, however, he will need to take them for life. His 11-year-old sister was lucky and didn’t get the faulty gene from her parents. For the three precious years of schooling he lost, his father has been desperate to get him readmitted. “School principals tell me that they would not like to take a risk with a child who was rusticated for bad behaviour,” says Manoj. “After pleading, the principal of his previous school agreed to take him on a trail basis.” Aditya was admitted to standard six in the month of June this year. His behaviour has been exemplary since and he is performing well in studies. “I even got a good remark from my teacher,” he says delighted. The varied mutant Experts in Europe have examined genetic defects of disease-affected patients and found 600 different mutations. This makes it very easy to isolate and diagnose. Given India’s large population, finding and mapping total number of mutations in the affected people requires large funding. Recently Dr Mohit Bhatt and his team, in collaboration with a German lab, identified three new Indian mutations of the disease. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Wilson's disease Hepatolenticular degeneration Last reviewed: September 10, 2010. Wilson's disease is an inherited disorder in which there is too much copper in the body's tissues. The excess copper damages the liver and nervous system. Causes, incidence, and risk factors Wilson's disease is a rare inherited disorder. If both parents carry an abnormal gene for Wilson's disease, there is a 25% chance in each pregnancy that the child will have the disorder. Wilson's disease causes the body to take in and keep too much copper. The copper deposits in the liver, brain, kidneys, and the eyes. The deposits of copper cause tissue damage, death of the tissues, and scarring, which causes the affected organs to stop working correctly. This condition is most common in eastern Europeans, Sicilians, and southern Italians, but may occur in any group. Wilson's disease typically appears in people under 40 years old. In children, the symptoms begin to show by age 4. Symptoms Abnormal posture of arms and legs Confusion or delirium Dementia Difficulty moving arms and legs, stiffness Difficulty walking (ataxia) Emotional or behavioral changes Enlargement of the abdomen (abdominal distention) Personality changes Phobias, distress (neuroses) Slow movements Slow or decreased movement and expressions of the face Speech impairment Tremors of the arms or hands Uncontrollable movement Unpredictable and jerky movement Vomiting blood Weakness Yellow skin (jaundice) or yellow color of the white of the eye (icterus) Signs and tests A slit-lamp eye examination may show: Limited eye movement Rusty or brown-colored ring around the iris (Kayser-Fleischer rings) A physical examination may show signs of: Damage to the central nervous system, including loss of coordination, loss of muscle control, muscle tremors, loss of thinking and IQ, loss of memory, and confusion (delirium or dementia) Liver or spleen disorders (including cirrhosis, splenomegaly, and liver necrosis) Lab tests may include: Complete blood count (CBC) Serum ceruloplasmin Serum copper Serum uric acid Urine copper If there are liver problems, lab tests may find: High AST and ALT High bilirubin High PT and PTT Low albumin Other tests may include: 24-hour urine copper test Abdominal x-ray Abdominal MRI CT scan of the abdomen Head CT scan Head MRI Liver biopsy The gene responsible for Wilson's disease has been found. It is called ATP7B. DNA testing is available for this gene. However, testing is complicated because different ethnic groups may have different changes (mutations) in this gene. Treatment The goal of treatment is to reduce the amount of copper in the tissues. This is done by a procedure called chelation -- certain medications can bind to copper and help remove it through the kidneys or gut. Treatment must be lifelong. The following medications may be used: Penicillamine (Cuprimine, Depen) binds to copper and leads to increased release of copper in the urine. Trientine (Syprine) binds (chelates) the copper and increases its release through the urine. Zinc acetate (Galzin) blocks copper from being absorbed in the intestinal tract. Vitamin E supplements may also be used. Sometimes, medications that chelate copper (especially penicillamine) can affect the function of the brain and nervous system (neurological function). Other medications under investigation may bind copper without affecting neurological function. A low-copper diet may also be recommended. Foods to avoid include: Chocolate Dried fruit Liver Mushrooms Nuts Shellfish You may want to drink distilled water because most tap water flows through copper pipes. Avoid using copper cooking utensils. Symptoms may be treated with exercise or physical therapy. People who are confused or unable to care for themselves may need special protective measures. A liver transplant may be considered in cases where the liver is severely damaged by the disease. Support Groups Wilson's disease support groups can be found at and Expectations (prognosis) Lifelong treatment is needed to control Wilson's disease. The disorder may cause fatal effects, especially loss of liver function and toxic effects of copper on the nervous system. In cases where the disorder is not fatal, symptoms may be disabling. Complications Anemia (hemolytic anemia is rare) Central nervous system complications Cirrhosis Death of liver tissues Fatty liver Hepatitis Increased number of bone fractures Increased number of infections Injury caused by falls Jaundice Joint contractures or other deformity Loss of ability to care for self Loss of ability to function at work and home Loss of ability to interact with other people Loss of muscle mass (muscle atrophy) Psychological complications Side effects of penicillamine and other medications used to treat the disorder Spleen problems Liver failure and damage to the central nervous system (brain, spinal cord) are the most common and dangerous effects of the disorder. If not caught and treated early, Wilson's disease is fatal. Calling your health care provider Call your health care provider if you have symptoms of Wilson's disease. Call a genetic counselor if you have a history of Wilson's disease in your family and you are planning to have children. Prevention Genetic counseling is recommended for people with a family history of Wilson's disease. References Kaler SG. Wilson's disease. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 230. Review Date: 9/10/2010. Reviewed by: Chad Haldeman-Englert, MD, Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. Logo of A.D.A.M. A.D.A.M., Disclaimer Copyright © 2011, A.D.A.M., Inc.

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