Wilson Disease Treatment in Hyderabad, India

Wilson’s disease is not usually easy to diagnose because of the multiple variations in clinical symptoms. Liver disease and cirrhosis are the two main characteristics of Wilson disease. Kayser-Fleischer rings, episodes of acute hemolysis, and mental disorders are frequently associated with acute liver failure.

Usually, after obtaining the patient’s entire medical and family history, the doctor diagnoses Wilson’s disease based on various diagnostic modalities such as:

• Physical examination
• Blood tests
• Urine tests
• Imaging tests and 
• Liver biopsy
  

Physical examination of Wilson’s disease

In general, the physician initiates examining a patient by using a stethoscope, and then he evaluates the signs pertaining to a particular disease. 

During a physical examination of a patient with Wilson’s disease, a gastroenterologist or hepatologist may examine 

• Eyes: the gastroenterologist or hepatologist will carefully evaluate patient’s eyes using a slit lamp to detect Kayser-Fleischer (KF) rings (type of brown or grey colored rings that encircle the cornea of the eye) and Sunflower cataract (clouding of lens in anterior capsule of the eye), jaundice (yellowish discoloration of eyes)
• Abdomen: abdomen of the patient will be evaluated to check the signs of liver damage such as: 
• Splenomegaly (enlargement of spleen)
• Ascites (build of fluid in the abdomen)
• Oedema (swelling caused by accumulation of fluid in various tissues) 
• Speech: to check the signs of mild dysarthria (difficulty in speaking)
• Central nervous system: the hepatologist may observe manifestations such as loss of memory, IQ, tremors, motor control (the mechanism by which the human body controls movement), coordination, and disorientation.
• Limbs: limbs are evaluated for the signs of bradykinesia (slowness of movement) and rigidity (prolonged, involuntary muscle contraction)
  

An authorized medical practitioner will draw blood from a vein for the blood test and send the sample to a laboratory. The hepatologist may prescribe one or more blood tests, including ones that measure the levels of the following:

• Serum ceruloplasmin: ceruloplasmin is a protein synthesized by the liver and is known for carrying copper into the blood and regulating iron breakdown. Low levels of ceruloplasmin may indicate Wilson’s disease. Usually, in healthy adults, the reference range for serum ceruloplasmin concentration is 20–40 mg/dL. The concentration of serum ceruloplasmin varies with age; typical neonates (newborn infants) have lower levels, that may rise by around six months and reach a maximum concentration between two and three years of age. After that, the levels steadily decline until adolescence. Moreover, several illnesses, including liver disease etc, can change the amount of serum ceruloplasmin.
• Serum copper: Most Wilson’s disease patients have lower copper levels than normal because copper is deposited into the organs rather than circulating in the blood. For copper in blood, the reference range is roughly 70–140 µg/dL. Serum copper levels in Wilson’s disease patients experiencing acute liver failure may be noticeably raised as a result of the metal being released from tissue reserves.
• Liver enzymes: Liver can become damaged over time if it is exposed to too much copper for it to store. Liver enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) can become abnormal due to damage to the liver caused by accumulated copper.
• Genetic testing: The hepatologist may also advise additional blood tests to detect abnormal gene that can cause Wilson’s disease.
• Complete blood picture: The count of red blood cells will be evaluated for the signs of anaemia. Severe spherocytic haemolytic anaemia (inherited blood disorder in which red blood cells become spherical shaped) can sometimes be an early sign of Wilson’s disease. A shortage of ceruloplasmin, the copper transport protein, causes excessive amounts of inorganic copper to accumulate in the bloodstream and mostly in red blood cells, which is the cause of haemolysis (destruction of red blood cells) in Wilson's disease.
• Relative exchangeable copper (REC): Wilson's disease can be detected using the REC test. Research found that compared to other conventional biochemical indicators for the diagnosis of Wilson’s disease, such as low blood copper or excessive urine copper excretion, the REC test is more sensitive and more specific.
• 24 urine collection tests: Wilson’s disease patients frequently have urine with higher-than-normal copper levels.

Patients with Wilson’s disease may have damaged renal tubules due to copper deposition resembling Fanconi syndrome. Furthermore, there may be an overabundance of amino acids, glucose, fructose, galactose, uric acid, phosphorus, and calcium excreted in the urine. There may be signs of proteinuria (proteins in urine), nephrolithiasis (kidney stones), and haematuria (blood in urine). A health care provider will equip patient with a specific, copper-free container to collect urine at home for a full day. Urine will be sent to a laboratory for analysis to determine the copper content by a medical specialist.

Imaging tests

Imaging studies are sometimes used by physicians (gastroenterologists and hepatologists) to look for indications of Wilson’s disease or other brain disorders in patients exhibiting symptoms related to the nervous system. Physicians could go for:

• Magnetic resonance imaging (MRI): A magnetic resonance imaging (MRI) test uses non-x-ray technology to take images of the body's soft tissues and internal organs. MRI offers insights into the pathologic and anatomic correlates of clinical signs and symptoms in Wilson's disorder in addition to biochemical data on the distribution of heavy metals in brain tissue.
• Computed tomography (CT) scan: CT scan generates images by combining computer technology and x-rays. The diagnosis of Wilson's disease cirrhosis can be aided by a computed tomography (CT) scan, by exhibiting findings more frequently than in other forms of cirrhosis. A few of these observations are: honeycomb appearance, dysmorphia, hyperdense nodules, liver density, and contour irregularity.
  

Wilson's disease liver biopsy

Liver biopsy is considered the gold standard test to diagnose Wilson’s disease. The hepatologist may opt for a liver biopsy if the outcomes of the blood and urine neither support nor deny the diagnosis of Wilson’s disease. Small samples of liver tissue will be removed by the hepatologist during a liver biopsy. A pathologist (a medical professional with specialized expertise in diagnosing illnesses by microscopic examination of tissues and cells) will use a microscope to evaluate the tissue in order to check for cirrhosis and liver damage, as well as to look for signs of particular liver disorders, including Wilson’s disease. To determine the tissue's copper content, a sample of liver tissue will be submitted to a laboratory.

Based on the progression of copper accumulation in the liver and other tissues, the Wilson’s disease may be categorized into four stages:

Stage 1: the liver's first copper buildup

Stage 2: Acute reorganization of copper in the liver, subsequent release of copper into the bloodstream

Stage 3: Persistent copper buildup in extrahepatic tissues, such as the brain

Stage 4: Chelation therapy is used to bring the copper balance back.

Differential diagnosis of Wilson’s disease

The clinical manifestations of Wilson’s disease are common with various other diseases, such as:

• Hepatitis (inflammation of liver)
• Haemolytic anaemia (disorder in which red blood cells are destroyed very rapidly)
• Parkinson's disease (central nervous system disorder which cause progressive neuron damage)
• Pantothenate kinase deficiency associated neurodegeneration [PKAN] (iron accumulation in the brain)
• Neuroacanthocytosis syndrome (disorder that causes progressive degeneration of basal ganglia of the brain and abnormally shaped red blood cells)
• Huntington's disease (a genetic disorder where brain nerve cells gradually degenerate)
  

For patients whose liver dysfunction worsens and leads to liver failure even with medication therapy, liver transplantation is recommended. For Wilson's disease liver transplant a multidisciplinary team such as a transplant surgeon, (hepatologist) transplant nurses, anesthesiologist, psychiatrist, dietitian, social worker etc, should work together to achieve a successful liver transplantation. 

Hepatologists consider several important aspects prior to a liver transplant to guarantee the best possible outcome for the patient. The hepatologist may evaluate factors such as: 

• Irreversible hepatic impairment: The patient should have an irreversible hepatic(liver) impairment that is predicted to be deadly in the absence of a transplant.
• Severity of the disease: When a patient’s liver function has substantially declined due to decompensated liver disease and encephalopathy (brain dysfunction), the decision to undergo a transplant is frequently taken into consideration.
• Cardiovascular (relating to heart and blood vessels) considerations: The perioperative (during surgery) care of advanced liver disease is complicated by the pathophysiologic consequences on the circulatory system. Therefore, it is necessary for a hepatologist to evaluate the patient’s cardiac health to avoid death related to cardiac complications.

• Psychological and interpersonal assessment: A wide range of concerns such as anxiety, financial worries, and whether family or friends are there to assist, following surgery should be evaluated.
  
• Blood tests: To determine a good donor match, these tests are considered by a hepatologist. They may also increase the likelihood that the body won’t reject the liver transplant.
  
• General tests: Tests such as lung function test, x-rays, colonoscopy, liver biopsy, etc. are considered to know the patient’s general health condition. In female patients with Wilson’s disease, the hepatologist may consider the evaluations such as pap test (cervical cancer screening test), mammogram (breast examination) and other gynecological considerations.