Prevention of Wilson's disease in asymptomatic patients.
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Biomedical subjects
Publications and source records attributed to I H Scheinberg.
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The uptake of radiocopper by HepG2 cells is a saturable, temperature-dependent and cellular energy-independent process with a Vmax of 7.1 +/- 0.2 pmoles min-1 mg protein-1 and an estimated Km of 3.3 +/- 0.5 microM. The rate of copper uptake is reduced at an equimolar concentration of albumin and is unaffected by zinc at a 10-fold molar excess. Approximately 70% of the newly incorporated radiocopper binds to membranes and organelles, while 30% is recovered in the cytosol. The soluble fraction can be resolved into two copper-binding protein peaks. Incubation of HepG2 with nonisotopic copper results in displacement of radiocopper associated with the proteins contained in the lower molecular weight peak. Exposure of the cells to cycloheximide inhibits the incorporation of the isotope into this fraction.
We report the terminal neurological impairment, amount of penicillamine taken, neuropathology and cerebral copper content of eleven patients with Wilson's disease treated for as long as 17 years. Therapy was accompanied by complete resolution of neurologic symptomatology in five patients and significant improvement in the neuro-psychiatric manifestations in six. Abnormal glial cells were seen in all the brains; gross or micro-cavitary changes were present in the putamina of eight. Of the four sets of observations, there was virtually no correlation between the degree of neurologic dysfunction - if any - in the months before death and either the amount of penicillamine taken or the cerebral copper content. There was, however, a fair degree of correlation between the severity of the neuropathologic findings and cerebral copper content.
D-penicillamine therapy can produce an unusual variety of skin lesions: Some are acute sensitivity reactions; some are caused by metabolic effects of the drug; some are due to autoimmune phenomena or to unknown mechanisms. The type and incidence of side effects depend on the original disease and on penicillamine dosage and duration of treatment.
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The author reviews the pathophysiology of the disorder and gives an historical perspective on intervention.