Wilson’s Disease + Hemochromatosis B&B

Question 1

how does the liver metabolize copper? (2 ways)

Answer 1

1. excrete in bile (most)
2. incorporated in ceruloplasmin and secreted into serum

both processes require ATP7B (hepatic copper transport protein)

Question 2

transport protein required to incorporate copper into ceruloplasmin

Answer 2

ATP7B - hepatic copper transport protein, incorporates copper into ceruloplasmin (secreted into serum) or excretes copper into bile

Question 3

what is the cause of Wilson’s Disease?

Answer 3

mutation of ATP7B (hepatic copper transport protein) gene on chromosome 13

—> lack of copper excretion into bile
—> hepatic copper accumulation, increased free radicals
—> increased free serum copper deposits in brain, cornea, kidneys, joints
—> low ceruloplasmin level* (ATP7B is required for copper incorporation)

*note, this causes a reduction in total serum copper despite copper overload

Question 4

what lab finding is the diagnostic hallmark of Wilson’s Disease?

Answer 4

mutation of ATP7B (hepatic copper transport protein) gene on chromosome 13

—> low ceruloplasmin level (ATP7B is required for copper incorporation)

note, this causes a reduction in total serum copper despite copper overload

Question 5

when and how does Wilson’s Disease present?

Answer 5

mean age is 12-23yo (takes time for damage from copper overload to occur)

—> liver cirrhosis, hepatocellular carcinoma
—> Parkinsonism, dyskinesia, dysarthria, tremor, behavioral disorders
—> hemolysis (Coombs-negative)
—> Kayser-Fleischer rings - diagnostic, detectable via split lamp exam

Question 6

what 3 tests are used to diagnose Wilson’s Disease?

Answer 6

aka genetic copper overload

1. low ceruloplasmin levels (ATP7B mutation prevents copper incorporation)
2. high urinary copper excretion (24 hours)
3. Kayser-Fleischer rings via slit lamp exam - found in nothing else

Question 7

treatment for Wilson’s Disease

Answer 7

aka copper overload (genetic)

tx = penicillamine: binds copper and promotes urinary excretion

Question 8

clinical use of penicillamine

Answer 8

treats Wilson’s Disease by binding copper and promoting urinary excretion

Question 9

what is needed for absorption of non-heme iron?

Answer 9

free iron, aided by vitamin C (converts Fe3+ to Fe2+)

Question 10

what is the specific genetic cause of hereditary hemochromatosis?

Answer 10

AR homozygous C282Y mutation (cysteine—>tyrosine) in the HFE gene on chromosome 6

may also have a combo C282Y/H63D mutation because both of these are common among Americans

mutation causes unregulated absorption of iron

Question 11

how does hemochromatosis present?

Answer 11

liver —> hepatomegaly, abnormal LFTs,cirrhosis, risk of hepatocellular carcinoma

pancreas —> diabetes

heart —> dilated cardiomyopathy

also joint pain, atrophy of testes, skin bronzing

Question 12

which 2 things should patients with hemochromatosis avoid in their diet and why?

Answer 12

1. alcohol - accelerates liver disease
2. vitamin C - increases absorption of non-heme iron

Question 13

liver biopsy with _____ stain can be used to diagnose hemochromatosis

Answer 13

Prussian blue staining - blue granules seen from iron deposition