GI Genetics

Question 1

short segment hirschprung disease

Answer 1

aganglionic segment does not extend beyond the upper sigmoid
80% of all cases

Question 2

long segment hirschsprung disease

Answer 2

aganglionosis extends proximal to the sigmoid

Question 3

clinical presentation of hirschprung disease

Answer 3

intestinal obstruction
colon distention from a lack of peristalsis
12% of cases are associated with Down syndrome
4:1 ratio male:female

Question 4

RET gene

Answer 4

provides instructions for producing a protein that is involved in signaling within cells including nerves in the intestine
mutations result in a nonfunctional version of the RET protein that cannot transmit signals within cells
w/o RET protein signaling enteric nerves do not develop properly

Question 5

iron overload

Answer 5

too much absorbed

too many erythrocytes are destroyed

Question 6

HFE

Answer 6

responsible for most common form of iron overload: hemochromatosis
fxn to regulate circulating iron uptake by regulating the interaction of TFR 1/2 with trasferrin

Question 7

HJV

Answer 7

responsible for most cases of juvenile hemochromatosis, rare but has sever iron overload

Question 8

TFR2

Answer 8

less common but with similar clinical presentation to HFE mutation
protein involved in the uptake of transferrin-bound iron into cells by endocytosis, minor role

Question 9

HAMP

Answer 9

hepcidin a iron-regulating hormone critical for absorption

Question 10

hepcidin

Answer 10

a key regulator of the entry of iron into the circulation

Question 11

transferrin

Answer 11

iron binding blood plasma glycoprotein that controls the level of free iron in biological fluids

Question 12

TFR1

Answer 12

protein required for iron import from transferrin into cells by endocytosis

Question 13

ferroportin

Answer 13

transmembrane protein that transports iron from the inside of a cell to the outside of the cell. inhibited by hepcidin results in the retention of iron

Question 14

iron deficiency

Answer 14

low hepcidin allows ferroportin to be active and pull Fe out of enterocytes and macrophages and put it in circulation

Question 15

iron overload

Answer 15

high hepcidin inhibits ferroportin which does not allow Fe to be pulled out of enterocyte and macrophages

Question 16

characteristics of hemochromatosis

Answer 16

late onset - 40 to 50 in males
non specific early symptoms
progresses to hepatosplenomegaly
liver fibrosis and cirrhosis
increasing liver damage leading to carcinoma
endocrinopathies
increased incidence of infections with infections with decreased hepcidin

Question 17

symptoms of hemochromatosis

Answer 17

pain in the knuckels of the pointer and middle finger called the iron fist

Question 18

hereditary hemochromatosis

Answer 18

C282Y 90% 
H63D
homozygous or heterozygous 
incomplete penetrance
northern european ancestry 1:250

Question 19

Menkels syndrome

Answer 19

ATP7A mutation
ABSORBTION
Cu uptake is impaired and a deficiency occurs

Question 20

Clinical presentation menkels syndrome

Answer 20

infant that is healthy until age two to three months, loss of developmental milestones, seizures
neurologic changes and concomitant characteristic changes of the hair (short, sparse, coarse, twisted, often lightly pigmented
vascular toruosity
laxity of skin
occipital horns

Question 21

Wilson disease

Answer 21

ATP7B
EXCRETION
mutations prevent Cu release from hepatocytes
apoceruloplasmin is degraded
ceruloplasmin levels decrease (excreted with bile)
Fe2/Fe3 levels affected

Question 22

clinical presentation of wilson disease

Answer 22

progressive lenticular degeneration
neurologic symptoms
psychiatric symptoms
Kayser-fleischer rings

Question 23

treatment for menkes syndrome

Answer 23

daily copper/histidine injections

Question 24

treatment for wilson disease

Answer 24

copper chelation