W

Wheezing-Infant

What is bronchiolitis?
What causes bronchiolitis?
Who gets bronchiolitis?
How do respiratory viruses cause disease?
What are the common findings in a child with bronchiolitis?
How is bronchiolitis diagnosed?
How is bronchiolitis treated?
What are the complications?
How can bronchiolitis be prevented?
What research is being done?

by Caroline B. Hall, M.D. 
Professor of Pediatrics, University of Rochester School of Medicine and Dentistry Rochester, New York

What is bronchiolitis?
Bronchiolitis is an infectious disease of the lower respiratory tract caused by a virus. It occurs in young children, usually within the first two years of life. Signs of an upper respiratory tract infection (a “cold”), as well as signs of a lower respiratory tract infection, characterized by wheezing, commonly accompany bronchiolitis. For this reason, bronchiolitis has sometimes been called “asthmatic bronchitis” or “wheezy bronchitis.”

What causes bronchiolitis?
Respiratory viruses cause bronchiolitis. Many common viruses, especially those that occur in the winter and spring, may cause bronchiolitis in young children. The most frequent cause of bronchiolitis is Respiratory Syncytial Virus (RSV). RSV causes outbreaks of bronchiolitis each year throughout most of the world. In North America, RSV causes regular outbreaks, lasting two to three months, which begin in the late fall or winter, and varying somewhat depending on the area of the country. In the warmer parts of the United States, the annual outbreaks tend to start slightly earlier than in the colder, more northern climates, which usually experience the beginning of an outbreak in November or December, with peak activity in January through March. Parainfluenza viruses, the second most common cause of bronchiolitis, also tend to occur in outbreaks, but at different seasons. Parainfluenza type 1 virus produces outbreaks in the fall every other year in the odd numbered years, while parainfluenza type 3 virus-which is the most common of the parainfluenza viruses to cause bronchiolitis-is prominent in the spring, but may last into the summer and fall. Occasionally, influenza also may cause bronchiolitis in young children during its winter to spring outbreaks. A number of other common viruses that cause respiratory infections, especially colds, may sometimes cause bronchiolitis in the young child. These respiratory viruses that cause the majority of bronchiolitis cases have two common characteristics: first, they are widespread viruses, which infect essentially all of us early in life and, sometimes, repeatedly throughout life. Second, these viruses each cause multiple types of respiratory illness, including upper respiratory tract infections, such as colds and ear infections, as well as infections of the lower respiratory tract, such as pneumonia, bronchitis, and laryngitis.

Who gets bronchiolitis?
Bronchiolitis is a common illness occurring in normal children during their first or second year of life, most frequently between 2 and 10 months of age. Younger infants and those who were born prematurely tend to have more severe illness. Children who are in day care during their first year of life are frequently exposed to respiratory viruses from their close contact with many other young children; therefore, they often have many respiratory infections during their first year. RSV spreads easily among groups of young children, and, in some, it may appear as bronchiolitis, while, in others, it may appear only as an upper respiratory tract infection. Children who are infected with RSV or with another of the bronchiolitis viruses may even become infected again in their second year of life with the same virus.

How do respiratory viruses cause disease?
The respiratory viruses that cause bronchiolitis are acquired from close contact with other individuals who are infected with the virus. Sometimes, these people show signs of illness, and, at other times, the infection may be very mild with few or no symptoms. The viruses, nevertheless, are still present in the secretions, and they are infectious when they enter the respiratory tract of a child via the eyes, nose, or, occasionally, the mouth. The spread of these viruses from individuals who are infected usually occurs from the small particles of respiratory mucus that are released from their sneezes or from touching their secretions that may be on used tissues or on other objects. When children rub their eyes or nose with hands contaminated by these secretions, the virus may enter the respiratory tract. In the lining of the nose and the upper respiratory tract, the virus multiplies and spreads down to the lower airways and lungs. During the initial few days, when the virus is multiplying, the child usually does not show any symptoms. Subsequently, however, the virus causes damage to the cells lining the respiratory tract, resulting in an excess of cellular material and secretions, which tend to obstruct the usual flow of air. Young infants are particularly vulnerable to this “plugging effect” because the diameter of their airways is small. The obstruction to their breathing tends to be most pronounced when they are exhaling, as the diameter of the airway is reduced more during the increased pressure needed for breathing out. A wheezy sound may be heard as the child forces the air through these areas of partial obstruction.

What are the common findings in a child with bronchiolitis?
Initially, bronchiolitis appears as an upper respiratory tract infection (i.e., a cold), with nasal stuffiness, a sore throat, and a slight cough. Fever, which is usually mild, but, occasionally, may be high, is frequent during these initial few days of the infection. Involvement of the lower respiratory tract usually appears two to three days later, and is characterized by the child developing a more prominent cough and the general signs of a worsening infection, such as irritability, decreased activity, and poor appetite. If the infection progresses further, the child may seem to have labored, fast, or wheezy breathing. The child may grunt with the effort of each breath, and the child’s chest muscles may retract between the ribs. Only the more severely ill children have labored breathing; most appear to have a bad cold with wheezy or croupy breathing. Whenever parents are concerned about a change in the sound, effort, or pattern of their child’s breathing, they should call their physician. For most infants, bronchiolitis lasts three to seven days. Although most show improvement within three to four days, a more prolonged cough and a gradual recovery period of one to two weeks or longer is common.

How is bronchiolitis diagnosed?
Bronchiolitis is diagnosed most frequently on its characteristic appearance in a child of the right age, especially when it occurs during the RSV season. For instance, a child within the first two years of life who develops a cold and wheezing during the winter months of peak RSV activity in a community is most likely to have bronchiolitis. Several other diseases, however, may appear similar to bronchiolitis. Asthma cannot always be easily differentiated from bronchiolitis, particularly if the child is having the first episode of wheezing. Furthermore, the two diseases may be combined since a significant proportion of wheezing episodes occurring in allergic or asthmatic children are initiated by a virus. Young children who have repeated episodes of bronchiolitis or wheezing are more likely to have asthma or an allergic background. Occasionally, the repetitive episodes of wheezing may be due to gastric reflux, a condition resulting from the tendency of some young infants to regurgitate stomach contents in the respiratory tract after feeding. Rarely, a child swallowing or choking on something that lodges in the respiratory tract and causes an obstruction of the airway will mimic bronchiolitis. The child’s physician may sometimes wish to get a chest x-ray or a measurement of the oxygen level in the blood to help confirm the diagnosis or severity of bronchiolitis. Secretions from the nose and throat may be tested for the presence of the respiratory virus causing bronchiolitis.

How is bronchiolitis treated?
The vast majority of children with bronchiolitis do well with no more than the usual care required for an infant with a bad cold. If fever is present, the usual medications to control it, such as acetaminophen and ibuprofen, should be used. The child should be encouraged to take an adequate amount of fluids. Solid food is less important. Alleviating the nasal stuffiness may help the child in taking fluids and in sleeping. Saline nose drops or other mild drops and suctioning, as advised by your physician, may help. Sometimes, a cold water humidifier in the child’s room may aid the nasal stuffiness caused by thick, dried secretions. In the more severely ill child with the signs of lethargy and difficulty in breathing, hospitalization may be required to administer additional oxygen or fluids if the child is dehydrated. Since a virus causes bronchiolitis, the antibiotics used for bacterial infections, such as strep throats and ear infections, are of no benefit. Viruses do not respond to such antibiotics. Currently, only one antiviral drug is approved for use for bronchiolitis caused by RSV. This drug, ribavirin, can be administered in a hospital by an aerosol into the child’s nose and mouth. Some children may be treated with bronchodilator drugs, which are aimed at reducing the airway obstruction, which occurs in some children, mainly those with allergies. Many infants with bronchiolitis, however, do not respond or have a variable response to bronchodilators. In most young infants, the major cause of the airway obstruction is the inflammation caused by the virus, rather than an abnormal reaction of the child’s airways. Corticosteroids have been evaluated in the treatment of bronchiolitis in an attempt to reduce the inflammation. However, carefully controlled studies have shown that they have no benefit in treating bronchiolitis, and the American Academy of Pediatrics does not advise the use of these drugs for bronchiolitis.

What are the complications?
Many studies of large numbers of children with bronchiolitis have shown that those infants who were most likely to have a complicated or severe case are those with underlying diseases, especially heart or lung disease. Additionally, those children who were born prematurely and those infants in the first few weeks of life are more at risk for prolonged or complicated illnesses. Infants who have the most severe illness may have such difficulty in breathing that they require assistance in their breathing with mechanical ventilation. Very young infants may have the complication of suddenly sping breathing for prolonged periods, called apnea. Such complications are generally rare, and the death rate from bronchiolitis is very low. The most common complication of bronchiolitis for children hospitalized with a more severe infection is recurrent episodes of wheezing within the first two years after discharge from the hospital. However, over the years, the frequency of these continued episodes of wheezing tends to decrease markedly. Most studies show that children who have had milder bronchiolitis, not requiring hospitalization, do not have this same degree of risk for recurrent episodes of wheezing.

How can bronchiolitis be prevented?
For most children, currently, there is not an effective way to prevent bronchiolitis. Since several very common respiratory viruses, especially RSV, cause bronchiolitis, contact with others who are infected is frequent and often is not recognized. Within the child’s family, spread of RSV and other respiratory viruses may be lessened by good hand-washing of the parents and other family members and by reducing an infant’s contact with secretions from an infected person (e.g., contaminated used tissues, shared toys, utensils, and other objects). Isolation of the child and interference with the child’s usual play and activities are usually of little value and should not be attempted for most normal children. For those few infants who are at a very high risk for complicated or severe infections from RSV, namely those who were born with significant prematurity and/or underlying lung disease, an additional means of prevention is available. A product containing a specific antibody to RSV has been approved for monthly administration to help prevent RSV infection in these high-risk children. This form of antibody against RSV has the advantage of being able to be administered once a month by intramuscular injection. In large, controlled studies, this product has been shown to decrease hospitalization from RSV infections in these high-risk infants.

What research is being done?
Since these respiratory viruses, especially RSV, produce so much illness in young children and are a major cause of medical visits and costs, much research currently is underway. This research is focused on developing effective vaccines to prevent RSV and to prevent infection with some of the other respiratory viruses, such as the parainfluenza and influenza viruses. Although a number of vaccines for the prevention of RSV have been tested in clinical trials, they have yet to be approved for general use. A number of vaccines, which contain live, but weakened, or inactive parts of the virus, appear promising and are being tested further. In addition, a number of antiviral drugs are being developed and tested for both preventing and treating the viruses that cause bronchiolitis.

References
Gruber WC: Bronchiolitis: In Long SS, Pickering LK, Prober CG, eds. Principles and Practices of Pediatric Infectious Diseases, 2nd edition, 1997: 246. * Hall CB, Hall WJ: Bronchiolitis. In: Mandell GL, Benett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, Fifth Edition. New York, NY: Churchill Livingstone Inc. 1999 (in press). * Hall CB, Hall WJ: Bronchiolitis. In: Hoekelman RA, Friedman SB, Nelson NM, Seidel HM, Weitzman ML ed. Primary Pediatric Care. Fourth Edition. St. Louis, MO: C.V. Mosby 1999 (in press). * These two references are also currently in the published editions: Hall CB, Hall WJ: Bronchiolitis. In: Mandell GL, Benett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, Fourth Edition. New York, NY: Churchill Livingstone Inc. 1994:612-614. Hall CB, Hall WJ: Bronchiolitis. In: Hoekelman RA, Friedman SB, Nelson NM, Seidel HM, Weitzman ML ed. Primary Pediatric Care. Third Edition. St. Louis, MO: C.V. Mosby 1997:1213-1216.
About the Author
Dr. Hall is board certified in pediatrics and the subspecialty of pediatric infectious diseases. She is also a Professor of Pediatrics and Medicine at the University of Rochester Medical Center. She has served on a number of national and government committees concerning infectious diseases and immunizations. Her major areas of medical research concern viral diseases of children, especially respiratory viruses, as well as other viral infections, such as HHV6 and HHV7, immunizations and epidemiology. Reviewed 11/3/2010
Copyright 2012 Caroline B. Hall, M.D., All Rights Reserved

Wilson Disease

What is Wilson disease?
Where does the copper come from?
If it is a copper disorder, why is it called Wilson disease?
What kind of gene is abnormal in Wilson disease?
What is known about the gene?
How is Wilson disease inherited?
Does Wilson disease occur more often in some populations than in others?
What kind of disease occurs with Wilson disease?
When does the disease begin?
What kind of liver disease occurs with Wilson disease?
What neurologic problems occur with Wilson disease?
Can Wilson disease affect other organs?
How is Wilson disease diagnosed?
Can Wilson disease be treated?
What is penicillamine and what does it do?
Is penicillamine a good treatment for Wilson disease?
What are the other treatments?
Are these the only treatments?
Is treatment lifelong or can it be sped at some point?
How should treatment be monitored?
Is a special diet necessary?
Are there any other treatment strategies?
What about liver transplantation for Wilson disease?
Is it okay to drink alcohol if a person has Wilson disease?
If a person has Wilson disease and gets pregnant, what should that person do about medication during the pregnancy?
If a person has Wilson disease, will that person’s children get it?
Since it is a genetic disease, what about family studies?
What research is being done?
Guide to technical words
Links

Eve A. Roberts, M.D., FRCPC
Division of Gastroenterology and Nutrition, Department of Pediatrics,
The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
What is Wilson disease?
Wilson disease (technical name: hepatolenticular degeneration) is an inherited disorder of copper handling in the liver. Copper is not packaged properly into its carrier protein in the liver, and it is not excreted efficiently into the bile. Consequently, copper accumulates in liver cells. When too much copper is in liver cells, it spills into the blood stream and is deposited in other organs, mainly the brain and the eyes.

Where does the copper come from?
Copper is found in many foods. Trace amounts are essential for good health, but too much copper can be toxic. Most people excrete the extra copper that they do not need, but persons with Wilson disease cannot do this adequately.

If it is a copper disorder, why is it called Wilson disease?
Wilson disease is named after an eminent neurologist, Kinnear Wilson, who first described the disease in 1912. Although born in the United States, he worked mainly in England. He described progressive neurologic disease in children in the same family, although he observed that some children also had liver disease. The ring of copper deposited in the eye, near the iris, called the Kayser-Fleischer ring, was described only a few years earlier. Copper’s role in damaging the liver was confirmed in the late 1940s. The genetic pattern of inheritance (called autosomal recessive) was determined in 1960. The gene that is abnormal in Wilson disease was identified in 1993. The technical name for this gene is ATP7B, but it also is called WND. The gene is located on chromosome 13.

What kind of gene is abnormal in Wilson disease?
The gene that is abnormal in Wilson disease (ATP7B) is the blueprint for a protein found mainly in liver cells but also in some brain cells and in certain parts of the kidney. In liver cells, this protein uses energy stored in the cell to move copper out of the cell, which is why the protein is called a “copper-transporter.” If the gene is abnormal, then the protein is not put together correctly and does not work.

What is known about the gene?
The gene is large, with over 80,000 base pairs organized in 22 coding units. By looking at the patterns in the gene, scientists can predict the features of the protein it makes. The protein has a tail of 6 units to bind copper and a zone to make a hole, or “pore” in a membrane, through which copper moves; it also has the mechanism for capturing cellular energy to fuel the whole process of transporting copper. This gene is complicated. Thus far, approximately 200 different mutations (or abnormal changes) in this gene have been identified.

How is Wilson disease inherited?
Autosomal recessive inheritance means that a person must have 2 abnormal versions of the WND gene to get the disease. The change that makes a gene abnormal is called a “mutation.” In Wilson disease, some people have 2 copies of the same mutation, but many people with Wilson disease have 1 copy of 2 different mutations. Either way, having 2 abnormal WND genes means a person has Wilson disease. If a person has only 1 abnormal gene, then that person is a carrier of the disease but does not get the disease. The parents of a person with Wilson disease are obliged to be carriers.

Does Wilson disease occur more often in some populations than in others?
Wilson disease is considered to be rare. It occurs worldwide at the rate of 1 per 30,000 population, meaning that the carrier rate is approximately 1 per 90 population, which is a relatively high rate compared to many inherited diseases. Wilson disease is found in all racial groups. In a few places, the rate of Wilson disease is unusually high; for example, in Sardinia off the coast of Italy, the disease rate is approximately 1 per 10,000 population.

What kind of disease occurs with Wilson disease?
Younger patients typically have signs of liver disease, and the liver disease can be highly variable. Many adult patients primarily have neurologic disease, usually with problems relating to movement. These patients usually have signs of liver damage. Some children and teenagers mainly develop neurologic disease. A minority of patients has only psychiatric symptoms. Although copper can be deposited in the eye, it does not disturb eyesight.

When does the disease begin?
Since Wilson disease is genetic, it is with a person from birth. Most people remain asymptomatic for years and do not know that they have Wilson disease. Children as young as 3 years can have severe liver disease from Wilson disease. Some adults develop only neurologic problems due to Wilson disease when they are in their fifth decade. In general, liver problems from Wilson disease become evident in people aged 5 through 40 years. Those persons with neurologic problems from Wilson disease become symptomatic when they are aged 10 through 55 years.

What kind of liver disease occurs with Wilson disease?
One of the complicated aspects about Wilson disease is that it leads to many different types of liver disease some severe, some not. At an early stage, Wilson disease may cause slight enlargement of the liver, possibly with extra fat in the hepatocytes. At a later stage, the liver becomes scarred or cirrhotic, often without any symptoms of liver disease. Patients with clinically evident liver disease can have an acute illness similar to viral hepatitis or resembling an autoimmune liver injury. Exceptionally, sudden and rapidly progressive liver failure can occur. This usually is accompanied by an abrupt and severe anemia, poor clotting function, changes in mental function (eg, stupor, coma), and renal failure.

What neurologic problems occur with Wilson disease?
Symptoms of Wilson disease affecting the nervous system are extremely variable, but with 2 main patterns. Movement disorders include tremors, involuntary movements, poor coordination, and loss of fine movements. Many patients actually have decreased movement; they get a stiffness of movement, mincing pattern to their gait, and loss of relaxed and spontaneous facial expression. They also may have garbled speech, drooling, and difficulty swallowing. In teenagers, excessive clumsiness, unexplained deterioration in school performance, and change in handwriting from large round letters to small jagged letters warrant consideration of Wilson disease. Personality or mood changes or depression may accompany these symptoms. Seizures are uncommon with Wilson disease. Intellect is normal.

Can Wilson disease affect other organs?
Copper can accumulate in the heart muscle and result in an abnormal heart rhythm. Copper overload in the pancreas can cause pancreatitis. Copper can cause red blood cells to break down (hemolytic anemia), leading to some jaundice. Gallstones also may result. Copper can interfere with various endocrine organs. In particular, women with Wilson disease may have difficulty becoming pregnant or have repeated miscarriages.

How is Wilson disease diagnosed?
Relatively simple blood and urine tests may be enough to determine whether or not a person has Wilson disease. The concentrations of copper and ceruloplasmin in the blood are low. The amount of copper excreted in the urine over 24 hours is higher than normal. Blood tests to determine liver function are performed. A computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain may be performed. The eyes should be examined carefully with a slit lamp to see if early Kayser-Fleischer rings are present. More complicated tests include sampling a small amount of the liver by a liver biopsy to examine the liver under the microscope and to measure the actual amount of copper in the liver tissue. Genetic testing can be performed with a blood sample to determine gene patterns that go with Wilson disease or to detect specific mutations.

Can Wilson disease be treated?
Wilson disease was one of the first liver diseases for which effective, lifesaving treatment was found. Currently, several possible treatments are available for Wilson disease. These treatments are the chelators, penicillamine and trientine, and the metallothionein-inducer, zinc. Other treatments are essentially experimental.

What is penicillamine and what does it do?
In use since 1956, penicillamine is a treatment for Wilson disease. It binds copper and increases the excretion of copper in the urine. This treatment may increase the amount of the safe storage protein for copper, called metallothionein, in liver cells. Penicillamine has other unrelated actions that include inhibiting the immune response and interfering with the formation of collagen (a protein in fibrous tissues). Although originally identified as a breakdown product of the antibiotic penicillin, this drug currently is manufactured by itself, without involving penicillin. Penicillamine may deplete vitamin B6 (pyridoxine) in the body; therefore, extra vitamin B6 is taken with it.

Is penicillamine a good treatment for Wilson disease?
Penicillamine has been a lifesaving treatment for Wilson disease since it first was discovered, and many specialists still regard it as the first-line treatment for Wilson disease. Although this treatment works for most people, it can have adverse effects, including fever and rash soon after starting the drug, damage to the kidneys causing protein to leak into the urine, problems with the bone marrow so that blood counts drop dangerously low, and complicated damage to numerous organs at the same time (ie, “lupus-like” drug reaction). Some patients who mainly have neurologic problems with Wilson disease get worse neurologically soon after starting penicillamine; this problem is usually, though not always, transient. A patient having any of these adverse effects may need to change to another treatment. The blood count and urinalysis have to be monitored whenever penicillamine is used. Some specialists believe that penicillamine is flawed as a treatment because of the potential for these adverse effects and advocate using other treatments.

What are the other treatments?
Trientine is a very different chemical from penicillamine, but it is also capable of binding copper and of increasing the amount of copper excreted in the urine. This treatment does not have the risk for adverse effects like penicillamine. When trientine is substituted for penicillamine, the adverse effects of penicillamine usually s. Anemia may develop because this drug also can bind iron, and, rarely, it may cause nausea because of stomach irritation. Trientine is not quite as strong a binder of copper as penicillamine, but, in day-to-day experience, this difference is not important. Zinc, taken in very high doses, removes copper from the body by increasing the amount of metallothionein in the cells lining the intestinal tract. Copper is bound within these cells and lost in the feces as these cells turn over every 3-5 days. Zinc is surprisingly strong and quite specific for eliminating copper from the body. This treatment has few adverse effects, but it can cause stomach irritation (gastritis).

Are these the only treatments?
A few other copper-binding agents have been tried and largely discarded from general use because they were unpleasant to take (eg, daily injections) or had unacceptable adverse effects. Some agents are still under development (eg, tetrathiomolybdate), which means that their effectiveness and adverse effects are not yet fully known. The safety and effectiveness of combining treatments also is not fully determined.

Is treatment lifelong or can it be sped at some point?
Most people can be treated satisfactorily with the currently available treatments (ie, penicillamine, trientine, zinc). Any of these treatments must be used daily for life. If a treatment has to be sped because it is causing an adverse effect, another treatment must be substituted. Sping successful treatment altogether inevitably leads to major deterioration. If treatment is started again, it may not work. In most cases, liver transplant then becomes the only effective treatment available.

How should treatment be monitored?
Most patients have follow-up visits twice a year to ensure that they are generally healthy. Their physician conducts a physical examination and monitors for adverse effects of drug treatment. Blood counts, liver tests, and urinalysis are performed, and the level of copper and ceruloplasmin in the blood is checked. The amount of copper excreted in the urine in 24 hours is checked approximately once a year to ensure that treatment is effective. A follow-up slit lamp examination of the eyes may be performed to see whether the Kayser-Fleischer rings disappear.

Is a special diet necessary?
Especially in the first year of treatment, foods that have very high concentrations of copper should be avoided. These foods are shellfish, nuts, chocolate, mushrooms, and organ meats (eg, brains, liver). Since the latter do not play an important role in the average North American diet, shellfish, nuts, and chocolate are the foods to target. Advice from a dietitian may be helpful and is mandatory for practicing vegetarians. Well water or water brought into the household through copper pipes should be checked for copper content. In general, municipal water supplies do not have to be checked. A water purifying system may be advisable if the copper content of the water is high.

Are there any other treatment strategies?
Copper may damage liver cells and other cells in the body by causing the formation of activated chemical intermediates. Antioxidants, such as vitamin E, may neutralize these chemicals. High doses of vitamin E may be used in addition to a drug to bind copper.

What about liver transplantation for Wilson disease?
Most patients with Wilson disease can be treated successfully just with medication, and liver transplant is not necessary. A few patients who do not respond to treatment require a liver transplant. The rare patient whose first sign of Wilson disease is acute liver failure requires immediate liver transplantation. Some patients on treatment who have very severe neurologic disease improve if they undergo a liver transplant, but, presently, the use of liver transplantation to treat the neurologic disease remains controversial. Patients who fail to comply with medical therapy may develop overwhelming liver damage, which can be treated adequately only by a liver transplant.

Is it okay to drink alcohol if a person has Wilson disease?
Alcohol can cause damage to liver cells that is similar in some ways to the kind of damage caused by copper; therefore, drinking alcohol is not advised in those persons who have Wilson disease.

If a person has Wilson disease and gets pregnant, what should that person do about medication during the pregnancy?
Although a small risk exists that the medication for Wilson disease will damage the baby, the greatest risk to the baby occurs if the disease is not well controlled during pregnancy. Therefore, taking the medication during pregnancy is important for those women with Wilson disease. Management of the pregnancy by a high-risk obstetrics team may be advisable depending on the severity of the underlying liver disease.

If a person has Wilson disease, will that person’s children get it?
Since Wilson disease is inherited by an autosomal recessive pattern, a person must have 2 abnormal genes to get Wilson disease. This means that if a person with abnormal genes marries a person with normal genes, the children inherit 1 abnormal gene and 1 of the mate’s normal genes. The children are carriers of the disease, but they do not have Wilson disease. If a person with normal genes marries a person who is a carrier of Wilson disease (ie, has 1 abnormal gene), then a 50-50 chance exists with each pregnancy that the child will have Wilson disease.

Since it is a genetic disease, what about family studies?
As soon as 1 child in the family is diagnosed with Wilson disease, all brothers and sisters should be tested. Each child has a 1 in 4 chance of being affected with the disease. Initial studies can be limited to a physical examination; blood tests of liver function; the concentration of copper and its carrier protein, ceruloplasmin, in the serum; and a measurement of the amount of copper excreted in the urine over a 24-hour period. If these studies are suggestive of Wilson disease, further studies may be required. Such studies may include a slit lamp examination of the eyes for Kayser-Fleischer rings, a liver biopsy, and CT scan or MRI of the brain. Since patients who begin treatment before they have any symptoms have the best prognosis, performing these studies is important. If the tests are inconclusive, they should be repeated several times, at 6- to 12-month intervals. If genetic testing is available, an excellent alternate approach is to use genetic testing to confirm who is affected and who is not. The genetic findings in the child with Wilson disease and parents can be used to guide the studies in the other children. Although a genetic approach provides the best data, because so many different mutations exist, it may be difficult to identify which mutation(s) are present in an individual family.

What research is being done?
Research is aimed at understanding as much as possible about the protein that is coded for by the ATP7B gene. Research is ongoing to identify as many mutations of the ATP7B gene as possible and to understand why Wilson disease is so variable as a clinical disease. Research also is focused on learning exactly how copper damages the liver and other organs so that even safer and more effective treatments for Wilson disease can be found. Because other inherited diseases involving copper overload occur, some researchers are studying the basis of those diseases.

Guide to technical words
Hepatolenticular degeneration: The scientific name for Wilson disease, without using the name of the physician who discovered it, meaning that the main damage is to the liver and to the lenticular area of the brain Ceruloplasmin: The protein in the blood that carries over 95% of the copper in the blood stream Metallothionein: A storage protein for copper and other metals inside of cells Chelator: Any chemical that binds a metal such as copper Mutation: A change in a gene leading to the abnormal function of the protein for which the gene codes Kayser-Fleischer ring: Deposit of copper in the eye, close to the iris; characteristic of Wilson disease but also found in other conditions with copper overload

Links
http://www.ninds.nih.gov/health_and_medical /disorders/wilsons_doc.htm http://www.medgen.med.ualberta.ca/database.html

References
Sass-Kortsak A. Wilson’s disease. A treatable liver disease in children. Pediatr Clin North Am. 1975;22:963-984. Scheinberg IH, Sternlieb I. Wilson’s disease. Philadelphia: WB Saunders; 1984. Walshe JM. Wilson’s disease presenting with features of hepatic dysfunction: a clinical analysis of eighty-seven patients. Q J Med. 1989;70:253-263. Danks DM. Disorders of copper transport. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Basis of Inherited Disease. New York: McGraw-Hill; 1995: 4125-4158. Roberts EA, Cox DW. Wilson disease. Baillieres Clin Gastroenterol. 1998;12:237-256. Sanchez-Albisua I, Garde T, Hierro L, Camarena C, Frauca E, de la Vega A, et al. A high index of suspicion: the key to an early diagnosis of Wilson’s disease in childhood. J Pediatr Gastroenterol Nutr. 1999;28:186-190. Wilson DC, Phillips MJ, Cox DW, Roberts EA. Severe hepatic Wilson’s disease in preschool-aged children. J Pediatr. 2000;137:719-722. Brewer GJ. Practical recommendations and new therapies for Wilson’s disease. Drugs. 1995;50:240-249. Sternlieb I. Wilson’s disease and pregnancy. Hepatology. 2000;31:531-532.
About the Author
Dr. Roberts obtained her medical degree from the Johns Hopkins University School of Medicine and trained in hepatology at The Royal Free Hospital under Professor Dame Sheila Sherlock. She is currently professor of paediatrics, medicine, and pharmacology at the University of Toronto and a hepatologist at the Hospital for Sick Children.
Copyright 2012 Eve A. Roberts, M.D., All Rights Reserved