Hepatolenticular degeneration

Penicillamine has also been used in cystinuria and for the treatment of rheumatoid arthritis. Discovery of its chelating properties led to its use in patients with Wilson s disease (hepatolenticular degeneration) and heavy-metal intoxications. Penicillamine is administered by mouth and should be taken on an empty stomach [4],... 

Two inherited human diseases that represent abnormal copper metabolism are Menkes syndrome and Wilson s disease. Menkes syndrome, with symptoms similar to those of copper deficiency, is characterized by a progressive brain disease, abnormally low copper concentrations in liver and other tissues, and diminished ability to transfer copper across the absorptive cells of the intestinal mucosa (USEPA 1980 Aaseth and Norseth 1986). Wilson s disease (hepatolenticular degeneration) is the only significant example of copper toxicity in humans. Wilson s disease is an autosomal recessive disorder that affects normal copper homeostasis and is characterized by excessive... 

Despite the positive effects of optimal levels of copper, deleterious effects may occur if a threshold level is exceeded. Wilson s disease (hepatolenticularic degeneration) is one of the diseases linked to the excess of copper in the body. It results from a dysfunction of the copper transmission process, which occurs due to a lack of suitable enzyme to catalyze the process of copper deletion from detached bonds with albumins and binding to ceruloplasma. The condition leads to neuron degradation, liver cirrhosis, and occurrence of colorful rings on the cornea (DiDonato and Sarkar, 1997). 

Pharmacology Wilson disease (hepatolenticular degeneration) is an inherited metabolic defect resulting in excess copper accumulation, possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper, but when their capacity is exceeded, copper is released into the blood and is taken up into extrahepatic sites. Treat this condition with a low copper diet and chelating agents that bind copper to facilitate its excretion from the body. Trientine is a chelating compound for removal of excess copper from the body. 

Penicillamine (Cuprimine) can be used to treat acute, severe rheumatoid arthritis, producing reductions in joint pain, edema, and stiffness. The response to penicillamine is usually delayed (4-12 weeks), and remissions can last several months after withdrawal of treatment. Radiographic evidence of this drug s efficacy is limited thus, penicillamine is seldom used to treat rheumatoid arthritis. The mechanism of action of penicillamine is unknown, but some evidence suggests that it may involve the inhibition of angiogenesis, synovial fibroblast proliferation, or transcriptional activation. Because penicillamine can chelate copper and promote its excretion, it is used to treat Wilson s disease (hepatolenticular degeneration) and has also been used in mercury and lead intoxication. 

It is indicated in metallic intoxication due to arsenic, mercury, gold, bismuth, lead, nickel, thallium and antimony in conjunction with sodium calcium edetate for lead poisoning. It is also useful in hepatolenticular degeneration (Wilson s disease). It is contraindicated in iron and cadmium poisoning. 

Penicillamine is used chiefly for treatment of poisoning with copper or to prevent copper accumulation, as in Wilson s disease (hepatolenticular degeneration). It is also used occasionally in the treatment of severe rheumatoid arthritis (see Chapter 36). Its ability to increase urinary excretion of lead and mercury had occasioned its use in outpatient treatment for intoxication with these metals, but succimer, with its stronger metal-mobilizing capacity and lower adverse-effect profile, has generally replaced penicillamine for these purposes. 

Metal—Wilson s disease (hepatolenticular degeneration), and hemo ehromutosis. 

Excessive levels of essential metal ions can be undesirable and chelation therapy may be needed for adequate control to be achieved. The treatment of patients suffering from Wilson s disease (hepatolenticular degeneration in which there is intracellular deposition of copper in the liver and brain, accompanied by a deficiency of the copper-containing protein, caeruloplasmin) is an example45. ... 

B40. Bush, J. A., Mahoney, J. P., Markowitz, H., Gubler, C. J., Cartwright, G. E., and Wintrobe, M. M., Studies on copper metabolism. XVI. Radioactive copper studies in normal subjects and in patients with hepatolenticular degeneration. /. Clin. Invest. 34, 1766-1778 (1955). 

Scheinberg, I. H., and Gitlin, D., Deficiency of ceruloplasmin in patients with hepatolenticular degeneration (Wilson s disease). Science 116, 484-485 (1952). 

Penicillamine (dimethylcysteine) is a metabolite of penicillin that contains SH groups it may be used to chelate lead and also copper (see Hepatolenticular degeneration). Its principal use is for rheumatoid arthritis (see Index). 

Hepatolenticular degeneration (Wilson s disease) is caused by a genetic failure to eliminate copper absorbed from food so that it accumulates in the liver, brain, cornea and kidneys. Chelating copper in the gut with penicillamine (p. 293) or trientine can establish a negative copper balance (with some clinical improvement if treatment is started early). The patients may also develop cirrhosis, and the best treatment for both may be orthotopic liver transplantation. 

Barbosa ER, Scaff M, Canelas HM. Degenera gao hepatolenticular. Avaliagao da evolufao neurologica em 76 casos tratados. [Hepatolenticular degeneration evaluation of neurological course in 76 treated cases.] Arq Neuropsiquiatr 1991 49(4) 399 04. 

Copper in Relation to the Progression of Wilson s Disease (Hepatolenticular Degeneration), Am, J. Pathol, (1968) 53, 883-901. 

D-Penicillamine (D-/6,/l-dimethylglycine), a metabolite of penicillin, was first isolated in the urine specimens from patients treated with penicillin with liver disease. It is an effective chelator of metals such as copper, zinc, and lead. It is used in the chelation therapy of Wilson s disease, which is characterized by excess copper accumulation leading to hepatolenticular degeneration (Chapter 37). 

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