Kayser-Fleischer rings, copper

FIGURE 46-7 Kayser-Fleischer ring in a young boy with Wilson s disease. The brown ring at the edge of the cornea is due to cornea] copper deposition. Courtesy of Dr Jorge Juncos (Emory University). 

The serum value for copper is increased. Some 80% of the absorbed copper is normally excreted via the bile in the stool. In prolonged cases of cholestasis, copper is deposited in other organs - even forming a faint Kayser-Fleischer ring on the cornea (as observed in Wilson s disease). The retained copper is not toxic, (s. p. 102)... 

Sht lamp eye examination may detect copper deposits in the eye (Kayser-Fleischer rings) and there may be abnormalities in liver frinction tests with an increased urine copper output (>500 fig Cu per L). Liver biopsy for copper analysis is useful in suspected cases and results above 250 fXg/g Cu dry weight are usually found (normal 8 to 40 Xg Cu per g dry weight). Failure of copper incorporation into plasma ceruloplasmin can also be demonstrated using an oral dose of stable Cu isotope. This may be helpful in excluding Wilson s disease when other tests are equivocal. Gene tracking and mutation detection are now possible, but since several hundred mutations exist this may not be informative. 

The classic clinical finding of increased copper deposition in the eye is the Kayser-Fleischer ring, caused by deposition of copper in Descemet membrane at limbus of the cornea. Although found in about 95% of patients with neurological or psychiatric manifestations, it is present in only about half of patients with hepatic forms of Wilson s disease" and is rarely present in children. As mentioned earlier, hemolytic anemia and renal failure commonly accompany acute forms of Wilson s disease hemolytic anemia may be episodic even in chronic forms of Wilson s disease. ... 

Plate 4 Copper imbalance causing Kayser-Fleischer rings of copper deposited in the outermost region of the cornea ofthe eyes. A genetic fault produces an inability to turn dietary copper into ceruloplasmin which, in turn, overloads the albumin low molecular mass aquated cupric ions system and results in copper compounds becoming deposited (see Chapter 3, Table 3.3. Treatment involves chelation therapy to remove as much of this excess copper as possible. Reproduced by permission from LG. Barrison, M.G, Anderson, and P.B. McIntyre, Gastroenterology in Practice , Gower Medical, 1992... 

In another rare inherited disorder, called Wilson s disease, excessive amounts of copper accumulate in liver and brain tissue. A prominent symptom of the disease is the deposition of copper in greenish-brown layers surrounding the cornea, called Kayser-Fleischer rings. Wilson s disease is now known to be caused by a defective ATP-dependent protein that transports copper across cell membranes. Apparently, the copper transport protein is required to incorporate copper into ceruloplasmin and to excrete excess copper. In addition to a low copper diet, Wilson s disease is treated with zinc sulfate and the chelating agent penicillamine (p. 123). Describe how these treatments work. (Hint Metallothionein has a greater affinity for copper than for zinc.)... 

All adole.scents or young adults wdth otherwise unexplained neurological or hepatic disease should be investigated for Wilson s disease, since this condition is fatal if not diagnosed and treated. Symptoms are a result of copper deptisi-lion in liver, brain, and kidney. Copper deposits in the eye can. sometimes be seen as a brown pigment around the iris (the Kayser-Fleischer ring). 

Once patients with this degree of tissue saturation are treated with penicillamine the progress of events is reversed, the liver regains its ability to trap copper (see Figure 4.6), the plasma is cleared more rapidly, the blood and urine copper levels fall and the kidneys regain their ability to acidify the urine [85]. Copper deposited in the cornea as the Kayser Fleischer rings can be seen to disappear. 

Brief mention has been made earlier of the ability of penicillamine to deplete the excess copper deposits in patients vsdth Wilson s disease. There are four main lines of evidence to support this contention (1) Visible copper deposits in the corneae, the Kayser Fleischer rings, can be seen to regress and finally disappear under the influence of treatment, only to reappear if this is interrupted or reduced to an inadequate level [78, 128]. (2) The concentration of copper in the plasma falls once treatment is established, in some cases it may fall to virtually undetectable levels [66, 129, 130]. (3) The concentration of serum caeruloplasmin falls, not only in patients with Wilson s disease [130], but also in patients with other diseases treated with penicillamine [131] (see Figure 4.7). (4) There is a fall in the basal excretion of copper in the urine... 

Kayser-Fleischer corneal ring (B. Kayser, 1902 B. Fleischer, 1903) occurs in Wilson s disease. It has also been observed in alcoholic liver disease. (47) Deposits of copper compounds form a brownish green comeal ring of 1 - 3 mm in width near the limbus. It can be identified at an early stage by slit-lamp examination, (s. fig. 4.17) Individual radiating, greenish brown sunflower cataracts are sporadically detectable in Wilson s disease. 

Wilson s disease can simulate Gilles de la Tourette s syndrome it must be excluded because it responds well to medical treatment. In addition to a movement disorder, Wilson s disease produces hepatic involvement, Kayser-Fleischer corneal rings, and abnormalities of serum copper and ceruloplasmin, which are absent in Gilles de la Tourette s syndrome. 

Wilson disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues. The hallmarks of the disease are the presence of hver disease, neurological symptoms and Kayser-Fleischer comeal rings. 

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