Wilson Disease: Expert Explains Why Sibling Screening Is Important

Mar 21, 2022, 13:02 IST

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Wilson’s disease or Wilson disease is a rare genetic condition in which copper builds up in the liver, brain, and other important organs. Wilson's disease is most diagnosed in people between the ages of 5 and 35, but it can also affect younger and older persons. Studies reveal that Wilson disease is the most common genetic cause of end stage liver disease in children, accounting for 35-55% of all cases and most parents are not aware of the cause and symptoms of this disease. “It is caused by mutations in the ATP7B gene which regulates copper balance in the body. Toxic accumulation of copper occurs first in liver and hence liver is virtually involved in all cases of Wilson disease, followed by brain and eyes. The disease is definitely not as rare as once believed to be. Prevalence of WD is approximately 1 in 10,000- 30,000 live births,” explains Dr Arti Pawaria, Consultant- Paediatric Hepatology & Gastroenterology at Global Hospital, Mumbai, who says the first patient of Wilson disease was reported in India in 1968 and since then medical field has witnessed several landmark changes in management of this disease.

Dr. Pawaria shares more insights on the condition and the necessity of early detection and treatment.

What The Study Says
Historically, it was considered a disease of patients aged 3 to 55 years. Between 2010-2020, the reported average age at diagnosis of Wilson disease in children in India was 9 years (range 3-15 years), which is similar to what the developed nations were reporting between 1970-2000. In developed countries, especially European countries and Korea, Wilson disease has been detected in children as young as 4 and 9 months of age, due to improved awareness about the disease. The fact that, in India, many patients still are missed due to the difficulty in early diagnosis and the lack of awareness about the true extent of the disease by health care providers undermines the need and urgency of creating awareness among doctors/physicians/people in our country.

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How It Affects The Organs
Liver is the first organ to be involved in Wilson disease predominantly presenting in childhood and running an invariably fatal course if not diagnosed early and treated adequately by pediatric hepatologist or gastroenterologist. Isolated liver involvement is more common in childhood and adolescence than adulthood. Wilson disease should be considered and ruled out by appropriate testing in all children presenting with any sign of liver disease ranging from acute liver failure, chronic liver disease, fatty liver or asymptomatic abnormality in liver function tests. In India liver failure and portal hypertension is still the most common presentation of Wilson disease in children mainly attributed to late diagnosis.

Wilson disease is treatable if detected in early stages and irreversible liver and neurological damage can be prevented. Initiating treatment early will result in rapid normalization of liver disease and normal life. An early diagnosis is very crucial to prevent evolution of the disease. If left untreated 20-30% of children with initial liver disease progresses to neurological and/or psychiatric manifestations at later age. Despite treatment many of the neurologically involved patients have worsening disease and become bed-ridden, unable to do activities of daily living.

Symptoms And Screening
Family members of a Wilson disease patient are at different risk at different stages hence it is essential to screen the family members. Because inheritance of Wilson disease is autosomal recessive, each brother/sister of a Wilson disease child is at 25% risk of having the illness themselves, which can become symptomatic at any time. Parents of a Wilson disease child also have 0.5% chance of having the disease even though they have been asymptomatic till adulthood.

Considering that on an average one family in India has 2 children, for every 100 Wilson disease children diagnosed with established liver disease, this can be identified in another 25-30 children in whom the onset of disease can be prevented. By early screening and diagnosis, lives of thousands of these young children can be saved from this otherwise devastating disease. Even within the same family there can be different presentation of Wilson disease from asymptomatic to full blown liver or/and neurological involvement. Hence, screening of sibling along with other family members should always be done using appropriate tests and immediate medical intervention.

All siblings of a child with Wilson disease should be screened for pre-symptomatic disease with liver function tests, serum ceruloplasmin, 24 hour urine copper, Kayser Fleischer ring on eye examination and/or targeted molecular analysis. Very effective and safe treatment is available for presymptomatic children identified through family screening. With strict follow up and good adherence to medicines, these pre-symptomatic children will have a normal life with normal liver functions.

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Diagnosis And Treatment
Definitive Wilson disease diagnosis is made using a balanced judgement among all tests (liver function tests, serum ceruloplasmin and 24-hour urinary copper, genetic mutation analysis, known as the Leipzig criteria) resulting in specific recommendations for the diagnosis and management of the disease. Genetic mutation analysis of the ATPB7 gene facilitates the diagnosis in borderline cases and are now widely available. Available treatments include chelation therapy and zinc salts, which reverse copper overload by different mechanisms. Indications for liver transplantation are rare (<1%) including patients with acute liver failure or those with progression of liver dysfunction to liver failure despite medical therapy. These children should be transferred to and managed in paediatric liver transplant center at the earliest.

With early diagnosis and treatment, the prognosis is good, however, an important issue is diagnosing patients before the onset of serious symptoms. Early accurate diagnosis and timely commencement of treatment are the best prospect for Wilson disease patients. Detailed counselling of the family regarding importance of strict adherence to the medical treatment and family screening without delay, especially of siblings, is the only way we can help children of our country from the devastating complications of this potentially treatable disease.

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