Kayser fleischer ring- wilson disease
Kayser fleischer ring - Wilson disease
Wilson disease is an autosomal recessive disorder. It is a neurodegenerative disorder that leads to reduced excretion of the copper from the biliary system and deposition of the copper in the liver and brain (basal ganglia). Wilson disease is also known as hepatolenticular degeneration.
The gene responsible for biliary excretion of copper located in the chromosome number 13.This gene will code for a copper transporting ATPase in the hepatocellular cell (hepatocytes). Mutation of this gene will interfere with the transport of the copper into the intracellular compartment. This will affect the conversion of the copper into the caeruloplasmin which is secreted later into the plasma or excreted into bile in the form of a copper. The excessive amount of copper inside the hepatocytes will lead to a damage of the hepatocytes mitochondria and release of the copper into the plasma which later deposited in another part of the body such as the brain, eyes and kidney.
Fulminant hepatitis and cirrhosis are commonly associated with excess accumulation of the copper. Accumulation of excess copper may also lead to renal tubular acidosis, hypothyroidism, movement disorder, neuropsychiatric disturbance, hemolytic anemia and arthropathy (pseudo gout).
Wilson disease is a rare disease with a strong family history or history of consanguinity. The carrier frequency of Wilson disease is 1 in 100 and the prevalence reported is around 1 in 30 000. The peak ages of presentation is 8 - 20 year and affect both sexes equally. However manifestation of the liver disease in Wilson disease is common in children less than 5 years old and neurological impairment is common in adult.
50% of cases are diagnosed incidentally with abnormal liver function test. Liver impairment such as hepatitis, cirrhosis, liver failure, jaundice, encephalopathy, easy bruising and variceal bleeding are common in young patient. Some patient may be asymptomatic. The neurological symptoms such as ataxia, dementia, drooling, dysphagia, dysarthria, dystonia, tremor, rigidity and dyskinesia are common in elderly patients. Besides that, an elderly patient may also present with neuropsychiatric symptoms such as schizophrenia and depression as well as psychosis, personality changes and conduct disorder. An elderly patient with Wilson disease may also present with chorea, in coordination and Parkinsonism symptoms.
On examination, the patient may present with jaundice, ascites, gynecomastia and hepatosplenomegaly. Examination of the eye may reveal the presence of sunflower cataract due to the accumulation of the copper on the lens. Keyser Fleischer ring or copper colored ring around the eyes are common and present as a green or brown ring on the corneal limbus /periphery of the cornea on the slit lamp examination.
The investigation requires can be divided into initial investigation and further investigation. Initial investigation may include full blood count, liver profile, serum copper and serum ceruloplasmin. Full blood count may reveal hemolytic anemia. Liver function test may reveal la high level of alkaline phosphate (ALP), alanine aminotransaminase (ALT) and aspartate aminotransferase (AST) as well as bilirubin due to the development of cirrhosis and hepatitis. Serum/plasma copper level is low. Plasma caeruloplasmin may also be low in 90% of patient with Wilson disease (<200mg/l). In certain cases such as acute inflammation (active hepatitis) serum ceruloplasmin may be normal as it is an acute phase protein. Kayser- Fleischer ring may be detected by slit lamp examination.
Further investigation may include 24 hours urinary copper level, liver biopsy and genetic analysis. 24 hours urinary copper level is performed when no diagnostic result is achieved with initial test but there is a high index of clinical suspicion of Wilson disease. A level of copper that is more than 100 microgram per 24 hours indicates the presence of Wilson disease. Penicillamine challenge is performed to confirm the finding. A liver biopsy is the next step requires in diagnosing Wilson disease if urinary and plasma copper level is non diagnostic. Wilson disease is confirmed if the concentration of the copper is more than 250 microgram/gram. The present of copper can be detected by using the rhodanine dye during liver biopsy. A liver biopsy is also important in the histopathological assessment of the liver tissue. Cirrhosis, hepatitis or fatty change can be identified with liver biopsy. Genetic analysis /screening is recommended for all first degree relatives of patient with Wilson disease. The screening /genetic analysis is involved in the measurement of serum ceruloplasmin.
The management of Wilson disease includes initial management, medical management and surgical management. The initial management includes educating the patient to avoid nuts, shellfish and liver. The medical management may include penicillamine, trientine, oral zinc sulfate and immunomodulator. Wilson disease is managed in a specialized unit. A copper chelator agent such as D- penicillamine or trientine is a useful copper chelating agent of choice. A patient who takes D- penicillamine agent 20mg/kg/day in conjunction with pyridoxine 20mg/day may require a lifelong treatment with slight deterioration of neurological states and require a regular monitoring of the liver function test. Trientine is another copper chelating agent which acts as an alternative to patient who is intolerant to penicillamine or severe neurological impairment due to penicillamine.
Oral zinc sulfate is the next form of treatment if penicillamine or trientine fail to reduce the copper stone. It is useful also for women of childbearing potential. The prescription of oral zinc sulfate with trientine or penicillamine is avoided as the effect will be neutralized. Oral zinc sulfate will stimulate the binding of copper with metallothionein in the intestinal cell. Immunomodulation such as 30 -40 mg/day of Prednisolone is initiated in patients with autoimmune like hepatitis until improvement in clinical state is achieved.
Surgical management may include liver transplantation. Liver transplantation is considered in a patient who is not responsive to medical treatment or the patient with end stage liver disease. Liver transplantation is also considered in patients with fulminant hepatic failure. General care for liver and neurological disease as well as regular monitoring of urinary copper is also important.
The complication of Wilson disease may include formation of gallstone as a result of hemolytic, cirrhosis and permanent central nervous system damage. Accumulation of copper may also induce renal tubular damage. The renal tubular damage may lead to renal tubular acidosis, phosphaturia, hypercalciuria and osteomalacia.
Early detection and treatment may improve the outcome. An asymptomatic state can be achieved with medical therapy. Psychiatric and neurological symptoms may respond to the treatment of the underlying disease. However some residual neurological deficit may persist and the present of liver disease may have a poor outcome.
kayser fleischer ring
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