Wilsons disease

The special interest is the determination of Fe, as the acceleration of sclerosed process is connected with the accumulation of Fe in this organ. Copper is accumulated in tissues at the genetic caused diseases (Wilson Disease, Hemochromatosis). This is the alteration in elemental ratios (e.g., Cu/Zn), that is the marker of pathological process. 

Wilson disease (MIM 277900) Mutations in the gene encoding a copper-dependent ATPase... 

Ceruloplasmin Binds Copper, Low Levels of This Plasma Protein Are Associated With Wilson Disease... 

Wilson Disease Is Also Due to Mutations in a Gene Encoding a Copper-Binding P-Type ATPase... 

The cause of Wilson disease was also revealed in 1993, when it was reported that a variety of mutations in a gene encoding a copper-binding P-type ATPase were responsible. The gene is estimated to encode a protein of 1411 amino acids, which is highly homologous to the product of the gene affected in Menkes disease. In a manner not yet fully explained, a nonfunctional ATPase causes defective excretion of copper into the bile, a reduction of incorporation of copper into... 

Treatment for Wilson disease consists of a diet low in copper along with Ufelong administration of penicillamine, which chelates copper, is excreted in the urine, and thus depletes the body of the excess of this mineral. 

Ceruloplasmin contains substantial amounts of copper, but albumin appears to be more important with regard to its transport. Both Wilson disease and Menkes disease, which reflect abnormahties of copper metabohsm, have been found to be due to mutations in genes encoding copper-binding P-type ATPases. 

Frydman,M.,Bonne-Tamir,B.,Farrer,L. A. etal.Assignment of the gene for Wilson disease to chromosome 13 Linkage to the esterase d locus. Proc. Natl Acad. Sci. USA 82 1819-1821,1985. 

El-Youssef, M. Wilson disease. Mayo Clin. Proc. 78 1126-1136, 2003. 

Brewer, G. J., Hedera, P, Kluin, K. J. et al. Treatment of Wilson disease with ammonium tetrathiomolybdate III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch. Neurol. 60 379-385, 2003. 

Figure 7.31 Schematic structures for Menkes and Wilson disease copper-transporting P type ATPases. (Adapted with permission from Figure 2 of Sarkar, B. Chem. Rev., 1999, 99(9), 2535-2544. Copyright 1999, American Chemical Society.)...

DiDonato, M. and Sakar, B. (1997). Review. Copper transport and its alterations in Menkes and Wilson diseases, Biochim. Biophys. Acta, 1360, 3-16. 

Wilson disease Treatment of patients with Wilson disease who are intolerant of penicillamine. 

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. 

Hypersensitivity There are no reports of hypersensitivity in patients given trientine for Wilson disease. However, there have been reports of asthma, bronchitis, and dermatitis occurring after prolonged environmental exposure in workers who use trientine as a hardener of epoxy resins. Observe patients closely for signs of possible hypersensitivity. 

Mineral supplements In general, do not give mineral supplements they may block the absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson disease. If necessary, iron may be given in short courses, but because iron and trientine each inhibit absorption of the other, allow 2 hours to elapse between administration of trientine and iron. 

K7. Kusuda, Y, Hamaguchi, K., etal. Novel mutations of the ATP7B gene in Japanese patients with Wilson disease. J. Plum. Genet. 45(2), 86—91 (2000). 

Wilsons disease copper chelation using penicillamine is efficient and effective. 

The main causes are hepatitis B and C, drug induced damage, metabolic disease (alcohol, haemochro-matosis and Wilsons disease) and autoimmune disease. Management depends upon the diagnosis. 

In the case of hepatitis associated with Wilsons disease D-penicillamine, initially 1.5-2 g daily is indicated, then reducing to half after one year. 

Strausak D, Mercer JF, Dieter HH, Stremmel W, Multhaup G. 2001. Copper in disorders with neurological symptoms Alzheimer s, Menkes, and Wilson diseases. Brain Res Bull 55 175-185. 

D-Penicillamine can promote the elimination of copper (e.g., in Wilson disease) and of lead ions. It can be given orally. Two additional indications are cystinuria and rheumatoid arthritis. In cystinuria, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In rheumatoid arthritis, penicillamine can be used as a basal regimen (p.332). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters p. 74), nephrotoxicity, bone marrow depression, and taste disturbances. 

The ethylene receptors localize to the endoplasmic reticulum (ER) membrane and the N-terminus is on the luminal side and the C-terminus is on the cytosolic side of the ER membrane.949 The transmembrane domains are responsible for formation of disulfide-linked dimerization950 and bind to ethylene with a copper cofactor that is provided by the RNA1 (Responsive to Antagonist l),951 a putative copper transporter similar to human Menkes Wilson disease protein. 

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