Irmin Sternlieb

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.

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 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.

Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis

Patients with Wilsons disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress‐induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor‐interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper‐induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury. (HEPATOLOGY 2004;39;963–969.)

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.

Effects of Anticopper Therapy on Hepatocellular Mitochondria in Patients with Wilson's Disease: An ultrastructural and stereological study

Liver biopsy specimens from 7 patients with Wilsons disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology. The characteristic mitochondrial abnormalities encountered in the hepatocytes of untreated patients were less pronounced or disappeared after treatment in 5 of the 7 patients. Simultaneously, relative mitochondrial volume, surface density of the external mitochondrial membranes, and the number of these profiles per unit area increased, whereas abnormal elevations SGOT and SGPT returned to normal levels.

Environmental treatment of a hereditary illness: Wilson's disease.

Excerpt INTRODUCTION Wilsons disease is the outcome of the interaction of an inherited defect and the environment. The inherited defect is an inability to synthesize a normal amount of the normal ...

Defective Urinary Acidification in Wilson's Disease

Abstract Four of 12 patients with treated Wilsons disease had subnormal urinary acidifying capacity, and one of them had bilateral medullary nephrocalcinosis characteristic of distal renal tubular...