What is Wilson Disease and What Are The Symptoms?

Wilson disease is a disease of copper metabolism. Wilson disease is an autosomal recessive disorder, which occurs due to mutation of ATP7B gene (which is a copper-transporting ATPase enzyme). The clinical manifestations of the disease are due to excess copper (toxicity of copper), especially in liver and brain. To make the treatment of Wilson disease effective, it is important to diagnose the disease early (as early as possible).

Pathogenesis of Wilson disease:

Mutation in ATP7B gene result in deficiency of ATP7B protein which cause impairment of excretion of copper through bile resulting in positive copper balance which get deposited in liver. Excess copper in liver is bound to metallothionein initially, but soon the copper exceeds storage capacity and liver damage initiates. Liver damage results in decreased level of ceruloplasmin in blood (in normal individuals copper is bound to ceruloplasmin in blood). As a result of decreased ceruloplasmin, free copper in blood increases, which is deposited in various tissues such as brain, which cause neurologic and psychiatric disorders.

What are the symptoms of Wilson disease?

Liver manifestations:

Patient with Wilson disease may present with hepatitis, cirrhosis, and other liver problems, usually in teenage years, but may be seen up to 4th or 5th decades of life. The hepatitis may be recurrent with or without jaundice. There may be hemolysis (breakdown of red cells of blood). Association of hemolysis and liver disease is a strong indication of Wilson disease as a diagnosis.

Brain manifestations:

Neurological manifestations of Wilson disease generally starts at early 3rd decade (early twenties), but may be delayed to 5th or 6th decades. There are three main movement problems in Wilson disease; they are tremor, in-coordination and dystonia (disturbance in muscle tone). These symptoms closely resemble Parkinsonism. Dysarthria and dysphagia are also commonly seen. Dystonia results in grotesque positions of the limbs, neck, and trunk. Other neurologic symptoms include orthostatic hypotension and sweating abnormalities, bowel, bladder, and sexual dysfunction, loss of memory, migraine-type headaches, seizures etc.

Psychiatric manifestations of Wilson disease includes behavioral disturbances such as temper tantrums, crying bouts, depression, hyperactivity, or loss of sexual inhibition etc. with onset generally five years prior to diagnosis.

Other manifestations of Wilson disease:

Females with Wilson disease may have amenorrhea (no menstruation) or frequent abortion. Stones in gall bladder and kidney are common problem. Osteoarthritis of knees is common. Increased urinary excretion of phosphates, amino acids, glucose, or urates may be seen as well as microscopic hematuria (blood in urine).

Eye manifestations of Wilson disease are sunflower cataracts and Kayser-Fleischer rings (copper deposits in the outer rim of the cornea).

How common is Wilson disease?                              

Wilson disease occurs with a frequency of 1 in 30,000-40,000. Children of diagnosed patient have a risk of Wilson disease 1 in 200, but siblings of a diagnosed patient have much higher risk of Wilson disease, 1 in 4.



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