wilson's disease

Question 1

The 2 main human disorders of copper transport

Answer 1

Menkes disease, an X-linked defect in transport of copper from the intestine that leads to generalized copper deficiency

Wilson disease, an autosomal recessive disorder of copper overload.

Question 2

Dietary copper is absorbed

Answer 2

in the proximal small intestine. Loosely bound to albumin, and also to histidine and α2- macroglobulin, copper is distributed to a variety of tissues.

Question 3

In the earliest stages, before cirrhosis develops,

Answer 3

histologic findings in the liver include steatosis, focal necrosis, glycogenated nuclei in hepatocytes, and sometimes apoptotic bodies.

Question 4

Early in the course of Wilson disease,

Answer 4

hepatocellular copper is bound mainly to metallothionein and is distributed diffusely in the cytoplasm of hepatocytes; therefore, histochemical stains for copper are negative.

Question 5

Hepatic Wilson disease has been identified

Answer 5

in toddlers and in patients older than age 60. Therefore, age is no longer a criterion for diagnosis.

Question 6

ALF of other etiologies, Wilsonian ALF typically features

Answer 6

disproportionately low aminotransferase levels (usually much less than 1500 U/L) at the onset of clinically apparent disease.

Question 7

The Kayser-Fleischer ring

Answer 7

is caused by copper deposition in Descemet’s membrane of the cornea.

Question 8

Diagnostics

Answer 8

The classic feature of a low ceruloplasmin concentration has proved less typical than previously thought, partly because hepatic inflammation may be sufficient to elevate serum ceruloplasmin levels.

Question 9

impressively low ceruloplasmin concentration (<10 mg/ dL) strongly

Answer 9

suggests Wilson disease.

Question 10

Aceruloplasminemia

Answer 10

has confirmed the important function of ceruloplasmin as a ferroxidase that oxidizes iron for transport from ferritin to transferrin.

Question 11

Three treatments for Wilson disease are generally recognized:

Answer 11

d-penicillamine, trientine, and zinc salts

Question 12

Diagnosis

Answer 12

If mutations have been identified in a patient, mutational analysis is easily carried out in first-degree relatives (siblings, parents, and offspring) by direct testing for the mutations found in the patient.