I. Herbert Scheinberg

Prevention of Wilson's Disease in Asymptomatic Patients

Abstract A biochemical diagnosis of Wilsons disease was established in 53 asymptomatic subjects, ranging in age from 15 months to 31 years. None had any pathognomonic physical sign of the disease. In 36 of these patients a liver biopsy specimen was examined by light microscopy, and in 31 histologic changes were found. Forty-two of these patients have been treated with a de-copperizing regimen, based on the continued and daily administration of D,L-penicillamine or D-penicillamine, and have remained asymptomatic during a period of observation of 142 patient years. An estimate, based on the natural history of Wilsons disease in 121 symptomatic patients, suggests that during this interval symptoms of the disorder could have been expected to develop in at least eight of these subjects.

D-penicillamine induced Goodpasture's syndrome in Wilson's disease.

Fatal pulmonary hemorrhages and rapidly progressive glomerulonephritis occurred in three patients with Wilsons disease (hepatolenticular degeneration) who had been treated with penicillamine for 2 to 31/2 years. Light microscopic studies of the kidneys showed severe glomerulonephritis with crescent formation, and the lungs showed intraalveolar hemorrhages. Although the clinical and pathologic abnormalities were those of Goodpastures syndrome, immunofluorescence microscopic studies in the one case tested showed an interrupted, rather than linear, fluorescence pattern.

DECREASED TASTE SENSITIVITY AFTER D-PENICILLAMINE REVERSED BY COPPER ADMINISTRATION

Abstract Treatment with D-penicillamine of 73 patients with scleroderma, cystinuria, rheumatoid arthritis, and idiopathic pulmonary fibrosis produced a decrease in taste sensitivity and/or hypocaeruloplasminaeia in 23. Withdrawal of D-penicillamine returned taste sensitivity and serum-caeruloplasmin to normal in those patients in whom it was decreased. Treatment with oral copper in the face of persistent D-penicilliamine treatment also returned taste sensitivity and serumcaeruloplasmin concentration to normal. These data indicate that copper plays a significant role in the physiology of taste.

Chronic Hepatitis As a First Manifestation of Wilson's Disease

Abstract In four males and three females, from 12 to 28 years of age, chronic hepatitis was diagnosed because of manifestations indistinguishable from those generally associated with this disease. ...

Lysosomal Defect of Hepatic Copper Excretion in Wilson's Disease (Hepatolenticular Degeneration)

After administration of 64Cu, striking differences were revealed in the copper content, specific activity, and protein binding of copper in the subcellular pools of hepatic copper in a woman with Wilsons disease compared with a control subject. None of the subcellular pools in the control subject could be identified as the source of the biliary copper, but the very low specific activity of 64Cu in lysosomes of the patient with Wilsons disease was virtually identical to that of the common duct bile and markedly different from all other subcellular pools. This suggested that lysosomes might be the source of biliary copper and that a lysosomal defect might account for the diminution of biliary copper excretion and the consequent hepatic accumulation of the metal in patients with Wilsons disease.

The existence of a second route for the transfer of certain glycoproteins from the circulation into the liver.

Abstract Oligosaccharide chains of agalactoorosomucoid, α 1 -acid glycoprotein from which sialic acid and galactose have been sequentially removed, terminate in N-acetylglucosaminyl residues. This protein is rapidly transferred from the circulation into the liver by a route distinct from that previously demonstrated for a number of galactosyl terminating glycoproteins.

Prognosis of Wilsonian chronic active hepatitis

Twenty of 320 patients with Wilsons disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilsons disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.

The Role of Radiocopper in the Diagnosis of Wilson's Disease

In patients with normal serum concentrations of ceruloplasmin, measurement of the incorporation of radiocopper into this protein can aid in the clinically important differentiation of patients with hepatic illnesses that mimic Wilsons disease from patients with this disorder.

Heterogeneity of Human Ceruloplasmin

Subfractionation of purified human ceruloplasmin, prepared from plasma of 9109 donors, has been carried out by chromatography on columns of diethylaminoethyl cellulose and hydroxylapatite. Electrophoretic analyses of these subfractions on starch gels, at pH 8.5 and 5.7, reveal the presence of at least four ceruloplasmins, two of which appear to differ in histidine content.

Skeletal Changes in Wilson's Disease: A Radiological Study

The authors have investigated the incidence and type of bone lesions in 38 patients with Wilsons disease (hepatolenticular degeneration) and correlated the radiographic findings with dysfunction of the central nervous system, liver, and kidneys. The skeletal surveys were considered normal in 5 patients, while 18 demonstrated demineralization alone. Nine showed subarticular cysts; fragmentation of bone about the joints was seen in 6, primarily in the hands, wrists, feet, and ankles.