Disease Pathogenesis and Genetics

Abstract

In this chapter we will go into some depth about how and why Wilson’s disease develops in a patient. We will begin by considering the evidence as to whether copper really is the culprit, and after concluding that it is, we will discuss normal copper handling and normal copper balance. We will then go into what has gone awry, in the broad sense. Is it enhanced copper absorption or decreased copper excretion? After concluding that it is the latter, we will discuss the evidence that the disease is caused by a failure of biliary excretion of copper, and how and why that may be happening. We will then discuss the genetic defect in Wilson’s disease, and how that defect may cripple copper excretion in the bile, thereby crippling copper balance regulation. Finally, we will discuss the natural history of copper accumulation and toxicity in various organs that leads to symptomatology.