Genetics

Question 1

What disorders have an mutated UDP - Glucuronyl Transferase (UGT)?

Answer 1

Breast Milk Juandice

Physiological Juandice of newborn

Crigler Najjar Syndrome

Question 2

Which mutation causes Dubin Johnson Syndrome?

Answer 2

MRP2 –> can’t transfer conjugated bilirubin into blood so it backs up in blood

Question 3

What type of inheritance is Crigler Najjar and what does it affect?

Answer 3

AR

Unconjugated hyperbilirubinemia

Affects metabolism of bilirubin –> increased unconjugated bilirubin

Question 4

Which type of Crigler-Najar (1 or 2) is more severe?

Answer 4

Type 1 –> lethal cause you can’t conjugate bilirubin at all.

So you get a lot of bilirubin depositing in the brain –> kernicterus

Question 5

What ezyme is completely defective in type 1 of Crigler Najjar Syndrome?

Answer 5

UGT1A1

(it converts unconjugated bilirubin to conjugated bilirubin)

Question 6

What are the main symptoms of Crigler Najjar?

Answer 6

Neonatal juandice… kids die young :(

Kernicterus (bilirubin in brain)

Question 7

What is the treatment for type 2 Crigler Najjar?

Answer 7

Phenobarbitol

Question 8

What is Gilbert’s Syndrome?

Answer 8

Isolated unconjugated hyperbilirubinemia WITHOUT hepatitis/hemolysis

Question 9

Instead of the entire UGT1A1 enzyme being defective like in Crigger Najar syndrome, what defect causes Gilbert’s syndrome?

Answer 9

Defect in the gene promotor for UGT1A1

Still leads to decreased UDP-glucoronyl transferase activity, therefore lower bilirubin uptake

Question 10

Gilbert’s syndrome is very common, therefore this would tell us that it is mainly asymptomatic, but what are some symptoms?

Answer 10

Associated w/ fasting

Stress (like med student)

Alcohol intake

Question 11

Patients w/ Gilbert’s syndrome don’t need any treatment. What is the only thing they have to lookout for?

Answer 11

They can’t take irinotecan meds.

Question 12

What mutation causes Rotor’s Syndrome?

Answer 12

Mutations in OATP1B1 + OATP1B3

Question 13

What substance is in excess with Dubin - Johnson and Rotor’s Syndrome?

Answer 13

Conjugated hyperbilirubinemia

Therefore, this means its not getting exreted properly and backs up in the blood.

Question 14

What characterizes Dubin-Johnson syndrome?

Answer 14

Black liver

Question 15

What characterizes Rotor’s syndrome?

Answer 15

Does not cause black liver

Patients usually asymptomatic and its rare

Question 16

What syndrome has elevated urine coproporphyrin levels?

Answer 16

Rotor’s Syndrome bitch

Question 17

When does breast milk jaundice appear?

When does breastfeeding juandice appear?

Answer 17

breast milk –> 2nd week of life

breast feeding –> 2-4 days of life

Question 18

What causes Wilson’s Disease?

Answer 18

Free copper accumulates in tissues.

Due to a mutation in ATP7B transporter protein

Question 19

What are the symptoms in Wilson’s disease?

Answer 19

Central Nervous System Problems

-parkinsons - like, flailing of arms (hemiballismus), dementia, cirrhosis

Kayser-Fleisher rings around eyes

Question 20

In Wilson’s disease, since the copper is building up inside the liver, what can this eventually lead to?

Answer 20

Liver diseases like hepatitis, cirhosis, cancer

Question 21

What is the treatment for Wilson’s disease?

Answer 21

A chelating agent that binds copper and removes it from the body (Penicillamine)