Heart Metal Transport Defects

Question 1

heavy metal transport defects discussed in this class

Answer 1

Hereditary hemochromatosis
Menkes Disease
Wilson Disease

Question 2

disease that deals with IRON transport

Answer 2

hereditary hemochromatosis

Question 3

disease that deals with COPPER transport

Answer 3

makes disease

wilson disease

Question 4

hereditary hemochromatosis

inheritance and incidence

Answer 4

autosomal recessive

high incidence rate (very common)

Question 5

hereditary hemochromatosis

genetic abnormality

Answer 5

caused by mutation on HFE gene on chromosome 6

missense mutation where try replaces cys

Question 6

hereditary hemochromatosis

enzyme affected

Answer 6

HFE gene codes for a cell surface protein product that binds the transferrin

Question 7

hereditary hemochromatosis

effect on substrate/byproduct

Answer 7

excess iron stored in multiple organs

Question 8

hereditary hemochromatosis

pathophysiology

Answer 8

switch of cys with tyr affects how HFE protein interacts with transferrin receptor (which plays an imp. role in iron iron homeostasis)

HFE disrupts the intestinal cell’s ability to sense iron levels causing excessive absorption from small intestine –> iron overload (DOES NOT involve transport)

increasing intracellular iron causes per oxidative injury inducing degeneration, cell death, and fibrosis formation

Question 9

hereditary hemochromatosis

clincial manifestation

Answer 9

excess iron stored in multiple organs (pleiotropic)

mc sign is cirrhosis of liver (jaundice)

cardiomyopathy, skin pigmentation, fatigue, and arthritis

classic symptom: Bronze skin

Question 10

hereditary hemochromatosis

expression, penetrance

Answer 10

delayed onset (earlier for males than females due to menses)

NOT expressed in infancy

Question 11

hereditary hemochromatosis

treatment

Answer 11

phlebotomy

may take years to deplete the storage

Question 12

menkes disease inheritance

Answer 12

x-linked

neurodegenerative disease of impaired COPPER transport

Question 13

menkes disease is of which element?

Answer 13

copper

Question 14

menkes genetic abnormality

Answer 14

Menkes gene (ATP7A) in Xq13.3

deletion in large segments = FRAMESHIFT

Question 15

menkes enzyme affected

Answer 15

protein responsible for copper transport and metabolism

Question 16

menkes effect on substrate or byproduct

Answer 16

normally keeps copper concentration low in cells SO will have high copper concentrations

Question 17

menkes pahophys

Answer 17

copper accumulation at LOW levels in liver, plasma, brain

higher than normal levels in kidneys and intestinal lining

Question 18

menkes clinical manifestations

Answer 18

neonates: hypothermia, hypoglycemia, jaundice, umbilical hernias, unusual hair pigmentation

2-2.5 months is when parents notice

development of progressive hypotonia (limp)

coarse wiry hair by 4-5 months

Question 19

menkes treatment

Answer 19

must be detected early before irreparable neurodegeneration occurs

bypass block in intestinal absorption of copper

copper replacement therapy

Question 20

wilson disease v. menkes gene

Answer 20

ATP7 for both, B in wilson, A in menkes

Question 21

Wilson Dz

genetic abnormality

Answer 21

mutation on ATP7B on chromosome 13

Question 22

Wilson Dz

enzyme affected

Answer 22

P type ATPase

Question 23

Wilson Dz

effect on substrate/byproduce

Answer 23

copper accumulation and toxicity to liver, brain, and eyes

Question 24

Wilson Dz

clinical manifestation

Answer 24

copper accumulation begins at birth, symptoms of disorder don’t appear until later in life

KAYSER FLEISHCER RING

Question 25

Kayser Fleischer ring

Answer 25

pathognomonic for wilson disease
deep copper colored ring at periphery of cornea

represents copper deposits

Question 26

Wilson Dz

treatment

Answer 26

requires lifelong tx w/ various copper chelating meds to remove excess copper form body (low copper diet)