Copper Balance Studies In Wilson's Disease

Abstract

A LTHOUGH it is generally recognized that Wilson's disease (hepatolenticular degeneration) is a genetic disorder involving a disturbance of the metabolism of copper, there are few reports related to studies of copper balance.1-3 Available data indicate that patients who have this disorder absorb greater than normal amounts of copper from the gastrointestinal tract 4 and excrete less than normal amounts in the feces.5 However, the mechanisms of intestinal absorption and fecal excretion of copper remain obscure, both in normal individuals and in patients with this illness.The treatment of Wilson's disease with penicillamine is known to increase the urinary excretion of copper.6,7 Likewise, it has been stated that the oral use of either ion-exchange resins 8,9 or potassium sulfide 10,11 at mealtime increases the fecal content of copper. In view of the derangement of copper metabolism in this illness, treatment should be aimed at achieving a negative copper balance, thus reducing the content of copper in brain, liver, and other tissues.Information derived from studies of the copper balance of patients who have Wilson's disease might be expected to help determine the relative effectiveness of D-penicillamine and of DL-penicillamine, the required dose of penicillamine, and the value of carbacrylamine resins (Carbo-Resin) and potassium sulfide as therapeutic adjuncts. Therefore, such balance studies were undertaken. Materials and MethodsCopper balance was studied in five cases of Wilson's disease. All five patients had Kayser-Fleischer rings, increased urinary excretion of copper, and decreased levels of serum ceruloplasmin concentration. Each was hospitalized in our metabolic unit during the studies. The components of the diets were weighed-that is, quantitative diets were used-during the various in¬ dividual studies. The diets varied from patient to pa¬ tient, and in some instances a different diet was used when a patient returned for other studies a year or two after the original study. Dietary copper was determined chemically in each instance by duplicate analyses of the diets used during the six-day study periods. Duplicate analyses for copper in the excreta were made from sixday pooled collections of stool specimens and from daily 24-hour collections of urine obtained during the six-day periods. Diets and excreta ware analyzed by a modifica¬ tion of the method of Martens and Githens I2 and that of Stone et al.13Digestion.-All urine, stool, and diet samples were digested on the micro-Kjeldahl apparatus. An all glass water-tip aspirator and a fume hood were used in this procedure. The acid fumes were drawn into the drain and washed down with copious amounts of water.Urine.-For each test, 25 ml of urine was placed in a 100 ml micro-Kjeldahl flask. To this was added 25 ml of concentrated HN03, 10 ml of 70% HCIO,, and some boiling beads. The flask was placed on a digestion hotplate, and the water was turned on to operate the aspirator. The mixture was watched carefully to see that the urine did not boil up into the nec...

Defective biliary excretion of copper in Wilson's disease

“…This is close to the figure of 676 ,ug/day for the mean diet-stool difference in Wilson's disease which I have calculated from the data in the literature (Cartwright et al, 1954;Bickel et al, 1957;Playoust and Dale, 1961;Sunderman et al, 1963;Goldstein et al, 1965;Canelas et al, 1967;Strickland et al, 1971). Diminished biliary copper excretion alone can therefore satisfactorily account for the positive copper balance of Wilson's disease.…”