Wilson’s Disease(Hepatolenticular Degeneration)

Wilson’s description of “Progressive Lenticular Degeneration: A Familial Nervous Disease Associated with Cirrhosis of the Liver” appeared in 1912.Wilson’s disease (WD) is an autosomal recessive inherited disorder of copper metabolism that may manifest with neurologic, psychiatric, and liver disorders, alone or in combination. It is caused by mutations in the gene encoding a P-type ATPase. WD has a worldwide prevalence of approximately 1 in 30,000, with a gene carrier frequency of 1 in 90. About half of WD patients (especially younger patients) manifest with liver abnormalities. The remainder present with neurologic disease (with or without underlying liver abnormalities), and a small proportion have hematologic or psychiatric problems at disease onset.

Neurologic onset usually manifests in the second decade with:

Wilson's Disease(Hepatolenticular Degeneration)

  • Tremor and rigidity
  • Parkinsonism with bradykinesia, dystonia (particularly facial grimacing)
  • Dysarthria, and dysphagia.
  • More than half of those with neurologic features have a history of psychiatric disturbances, including depression, mood swings, and overt psychosis.

Kayser-Fleischer (KF) rings are seen in 80% of those with hepatic presentations and virtually all with neurologic features.They consist of a characteristic grayish rim or circle at the limbus of the cornea and are best detected by slit-lamp examination.
Neuropathologic examination is characterized by neurodegeneration and astrogliosis, particularly in the basal ganglia.
WD should always be considered in the differential diagnosis of a movement disorder in a child. In both the typical and variant forms of the disease, the finding of a low serum ceruloplasmin level (less than 20 mg/dL in 80 to 90 percent of patients), low serum copper (3 to 10 mM/L; normal 11 to 24 mM/L), and increased urinary copper excretion (more than 100 mg Cu/24 h) corroborate the diagnosis. CT brain scan usually reveals generalized atrophy in established cases and 50% have hypointensity in the caudate head, globus pallidum, substantia nigra, and red nucleus. MRI shows symmetric hyperintensity on T2-weighted images in the putamen, caudate, and pallidum
Wilson's Disease(Hepatolenticular Degeneration)1
Nevertheless,liver biopsy with demonstration of high copper levels remains the gold standard for the diagnosis.

In the absence of treatment, the course is progressive and leads to severe neurologic dysfunction and early death

Treatment is directed at reducing tissue copper levels and maintenance therapy to prevent reaccumulation.. Penicillamine is frequently used to increase copper excretion, but it may lead to a worsening of symptoms in the initial stages of therapy. Side effects are common and can to some degree be attenuated by coadministration of pyridoxine. Tetrathiomolybdate blocks the absorption of copper and is used instead of penicillamine in many centers. Trientine and zinc are useful drugs for maintenance therapy. Effective treatment can reverse the neurologic features in most patients, particularly when started early. Some patients stabilize and a few may still progress, especially those with hepatocerebral disease. KF rings tend to decrease after 3–6 months and disappear by 2 years. Adherence to maintenance therapy is a major challenge in long-term care.
Many wilsonian patients with advanced liver disease have been subjected to liver transplantation, which is curative for the underlying metabolic defect. The degree of neurologic improvement varies; in some it has been remarkable and sustained, confirming that the hepatic defect is primary and that the brain is involved secondarily.
An important aspect of treatment is the screening of potentially affected relatives for abnormalities of serum copper and ceruloplasmin; if any relative is found to have the disease, penicillamine should be given indefinitely to prevent the emergence of neurologic symptoms. A full explanation of the dangers of ceasing the medication must be given, and compliance may have to be monitored.