Kayser-Fleischer ring

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). 

Wilson s disease Onset during childhood or early adulthood, liver disease, involuntary problems, Kayser-Fleischer rings during eye examination... 

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... 

While many of the patients develop the full-blown clinical picture of the disease with involvement of the nervous system, liver, and kidney and with Kayser-Fleischer rings, a substantial number may have neurological... 

U6. Uzman, L. L., and Jakus, M. A., The Kayser-Fleischer ring. A histochemical and electron microscope study. Neurology 7, 341-355 (1957). 

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). 

Descemefs membrane in the cornea, producing a Kayser-Fleischer ring and also as azure lunulae in the finger nails. Hepatocellular carcinoma is a rare consequence of Wilson s disease (Loudianos et al. 2000). 

Sussman, W. Scheinberg, I.H. Disappearance of Kayser-Fleischer Rings. Effects of Penicillamine, Arch. Opthal., 1969, 82, 738-741. 

Fig. 21.2 Kayser-Fleischer ring in a 15 year old patient with neurological Wilson disease (See also Color Insert)...

Most patients with Wilson disease, whatever their clinical presentation, have some degree of liver disease. Chronic liver disease (if undiagnosed and untreated) may precede manifestation of neurological symptoms for more than 10 years. Patients can present with liver disease at any age. The most common age of hepatic manifestation is between 8 and 18 years, but cirrhosis may already be present in children below the age of 5. On the other hand, Wilson disease is diagnosed also in patients presenting with advanced chronic liver disease in their 50s or 60s, without neurological symptoms and without Kayser-Fleischer rings. 

Kayser-Fleischer rings by slit lamp Present - In up to 40% of patients with Hepatic Wilson disease - In most asymptomatic siblings Primary biliary cirrhosis... 

Diagnosis is far more complex in patients presenting with liver diseases. None of the commonly used parameters alone allows for a definite diagnosis of Wilson disease. Usually a combination of various laboratory parameters is necessary to establish the diagnosis. Kayser-Fleischer rings may be absent in up to 50% of patients with Wilsonian liver disease and even in a higher proportion in fulminant Wdson disease. Kayser-Fleischer rings can occasionally be detected in patients with primary biliary cirrhosis. 

Kayser-Fleischer-ring 640 Kelley-Seegmiller syndrome 452 Ketoacidosis 197, 200, 312 Ketosis/ketotic 63, 70, 170, 198, 200... 

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