Degeneração hepatolenticular

Abstract

The history of hepatolenticular degeneration started with the cases of "pseudosclerosis" reported by Westphal described the clinical manifestations and the pathological findings, emphasizing the frequently asymptomatic liver cirrhosis, and stressing the familial incidence of the disease; he named it progressive lenticular degeneration. Wilson refutedPresented to the First Pan-American Congress of Neurology (Lima, Peru, October 1963 Full-term pregnancy, nor mal birth. She frequented primary school in a satisfactory way. At the age of 10 years, she had jaundice, which waned spontaneously; she suffered from occa sional epistaxes.The physical, intellectual and gregarious development was normal until the age of 12, when she began to present shaking of the four limbs, followed by progressive disturbance of equilibrium and speech, as well as mental impairment. Only 3 menses untill the age of 16. She does not know a similar disease in her family; she has an elder brother and a younger sister, both healthy.Good general conditions. Hyperhidrosis. Liver and spleen not palpable. Disor ders of behavior and humor, with exhibitionism and crises of aggressivity.Wilsonian facies, with mid-open mouth, slight protrusion of tongue, and "spastic" smile. Normal praxia and language. The patient could not stand.Active movements were present but they were restrained by a marked elastic stiffness in flexion, es pecially in the lower limbs, with painful crises of aggravation. His relatives informed that the patient was in good health untill the middle of 1959, when he suffered a fall owing to a transient lack of consciousness. Soon afterwards he began to display speech disorders, lack of interest for his customary activities, and crises of excitation.He was admitted to an inland hospital, where he stayed for 45 days in drowsiness. When his conditions did further deteriorate, he was removed to the emergency ward of our hospital, and admitted to the Neurologic Department 5 days later. The familial history could not be ascertained.Good physical development; slight jaundice; liver and spleen not palpable. The patient was unconscious, reacting only to painful stimuli. He exhibited spontaneous and pain-induced movements.Waxy stiffness with the cog-wheel phenomenon in the four extremities.The deep reflexes of the limbs were absent, while the orbicularis oris and naso-palpebral reflexes were hyperactive; the Babinski sign was present firstly on the left and later on the right too; the abdominal reflexes were absent; the cough, swallowing, and corneo-palpebral reflexes were present. The patient had a tremor with a parkinsonian rhythm, but with greater amplitude, in the left limbs, especially in the upper left extremity. Bilateral Kayser-Fleischer corneal rings. The results of laboratory examinations are summarized in tables 1 to 4, and the study of copper metabolism in table 7. Soon after admission hyperthermia appeared and the general conditions went worse. In 12-1-1961 hematuria and tracheobronchial oversecretion were noted, the patient dying i...

Wilson's Disease

“…Copper and necrosis have also been seen in'the cytoplasm of renal tubular epithelium of five patients dying of Wilson's disease (65), and the pathologic renal physiology seen in the illness is chiefly, though not wholly, tubular (66). An unusual flattening of the immediate post-glomerular proximal tubule has been reported by Kark in a biopsy from one patient (67), but neither this abnormality nor any other apparently primary change has been seen in 20 biopsies from other patients (2,9,15,68,69). Further, Morgan and his col laborators believe pharmacologic removal of copper may have improved at least some manifestations of tubular dysfuntion in their patient (69).…”

“…It has been reported from Europe and North America (4,7,8), from the Caribbean and South America (2,9), from China, Japan and Viet-Nam (10--14), from Australia (15), from India (16), and from Israel (17). One mutation to an abnormal "Wilson's disease allele" of a normal "copper balance gene" and emigration in succeeding generations (2,4,16) could account for such a widespread geographic distribution.…”

“…It has been reported from Europe and North America (4,7,8), from the Caribbean and South America (2,9), from China, Japan and Viet-Nam (10--14), from Australia (15), from India (16), and from Israel (17). One mutation to an abnormal "Wilson's disease allele" of a normal "copper balance gene" and emigration in succeeding generations (2,4,16) could account for such a widespread geographic distribution. But the case material in the reports from Asia, India, and America (4,6), and the existence of Wilson's disease in inbred Yemenite Jews who have been ethnically segregated for 2000 years (17), make it virtually certain that several such mutations have occurred.…”

“…Where the family history and clinical findings are not posi tive we have suggested that a subject be considered homozygously abnormal if there are deficiency of ceruloplasmin and an elevation of hepatic copper concentration (23), although we now consider 250 ",gig of dry liver as the critical level of the latter. Patients also appear to have nondiagnostic ab normalities in their fingerprints (28); aneuploidy and abnormalities of the X chromosome have been observed in one family (29); and one patient has been shown to possess a normal chromosomal pattern (2). An individual is seen very rarely in whom the diagnosis can neither be made nor excluded despite investigations of all criteria of the disease (30).…”

“…Consequently, a patient with Wilson's disease must certainly have been in greater positive copper balance than normal since birth, if not before. But the net average quantity of copper which must be retained from a daily intake of several milligrams to account for the amounts of copper seen in organs of young adult patients is about SO J.Lg-far too little to be measurable either by balance studies using con ventional methods (2,15,(71)(72)(73)(74) or radioactive copper (75)(76)(77), as has been critically pointed out by Cartwright (71) and Bickel (31) and their collab orators. Nevertheless, estimates and comparisons of absorption of orally ingested radioactive copper6• have been made by determining either the subsequent serum concentrations of the isotope as a function of time (27,75,78), or the amount of copper64 appearing in the urine (76).…”