Kayser-Fleischer ring

**Definition:** A KF ring is a circumferential golden-brown, green, or rust-colored ring at the corneal limbus. Copper deposits in Descemet's membrane. It often starts at the superior and inferior poles. Early or subtle rings may need slit-lamp examination or gonioscopy to see. Advanced rings may be visible to the naked eye.

**Pathophysiology (Wilson disease):** - Autosomal recessive mutation in ATP7B on chromosome 13. It encodes a copper-transporting P-type ATPase in hepatocytes. - Impaired biliary copper excretion and impaired incorporation of copper into apoceruloplasmin cause copper accumulation in the liver. - Reduced ceruloplasmin (holoceruloplasmin) results in low serum ceruloplasmin. - Once hepatic storage is saturated, copper spills into the circulation and deposits in the brain (basal ganglia, especially the putamen/lenticular nuclei), the cornea (KF rings), and the kidneys.

**Clinical features of Wilson disease:** - Hepatic: acute or chronic hepatitis, cirrhosis, acute liver failure with Coombs-negative hemolytic anemia. - Neurologic: parkinsonism, tremor ("wing-beating"), dystonia, dysarthria, dysphagia, and ataxia. - Psychiatric: depression, personality change, psychosis. - Ocular: KF rings. Sunflower cataracts are less common. - Renal: Fanconi syndrome and renal tubular acidosis. - Other: osteoporosis and arthritis. - Presentation is typically age 5–35.

**Diagnosis:** - Low serum ceruloplasmin. - Increased 24-hour urinary copper excretion. - Increased hepatic copper on biopsy (gold standard). - Slit-lamp exam for KF rings. - Genetic testing for ATP7B. - The Leipzig score integrates these findings.

**Treatment:** - Copper chelators: D-penicillamine (can cause nephrotic syndrome, lupus-like syndrome, and myasthenia) or trientine. - Zinc, which induces intestinal metallothionein and blocks copper absorption, is used for maintenance. - Liver transplant for fulminant disease or decompensated cirrhosis. - Avoid high-copper foods such as shellfish, nuts, liver, and chocolate.

**High-yield pearls:** - Present in about 95–99% of Wilson patients with neurologic or psychiatric symptoms but only about 50% with hepatic-only presentation. Their absence does not rule out Wilson disease in a hepatic presentation. - They are not entirely specific for Wilson disease. They can occur in chronic cholestatic liver diseases such as primary biliary cholangitis, primary sclerosing cholangitis, and neonatal cholestasis, and in cryptogenic cirrhosis. - Rings may regress with chelation therapy. - Think "ATP7B = Copper Bad": a defect in ATP7B leads to copper buildup. - Classic board vignette: a young patient with tremor, behavioral change, and liver disease. The eye exam shows KF rings, and labs show low ceruloplasmin. - Differential for movement disorder plus liver disease: Wilson disease vs. hemochromatosis (iron, with a different presentation) vs. acquired hepatocerebral degeneration.