10. Genetics of GI Disorders Flashcards
What are clues to Crigler Najjar in a vignette
- Infant
- Yellow color
- Behavior changes
- Arms just flopping
- Inbred (recessive trait)
Crigler Najjar is a mutation in what gene
UGT1A1
Type 1- no expression or absence
Type 2 (Arias)- defective or less active form of gene
What is Kernicterus
-Bilirubin deposition in the brain
-Poor development/mental function
(Caused by Type 1 Crigler-Najjar)
What are treatments for Crigler-Najjar
- Plasmapheresis
- Phototherapy
- Phenobarbital (UGT1A1 inducer) for Type 2 only
- Liver Transplant
What are the genetics behind Gilbert’s Syndrome
Defect in the promoter of UGT1A1
What is a classical presentation of Gilbert’s
Occasional mild jaundice during fasting, stress and alcohol intake
How can Gilbert’s be diagnosed
- Unconjugated hyperbilirubinemia without evidence of hepatitis or hemolysis
- Fasting Test (specific for Gilbert)***
- Rifampin Test
What can be done to help patient’s with Gilbert
Mostly asymptomatic so no need treatment
Avoid Irinotecan (certain meds)
What are the genetics behind Dubin-Johnson
Mutation in MRP2
What causes the black liver in Dubin-Johnson
Impaired excretion of epinephrine metabolites
What are the genetics behind Rotor’s Syndrome
Mutations in BOTH OATP1B1 and OATP1B3
How might a Rotor patient present
Elevated urine Coproporhyrin levels
May become jaundice or icteric during fatigue, pregnancy or with oral contraceptives due to a reduction in hepatic excretory function
What are the genetics behind Wilson’s Disease
Mutation in ATP7B
What occurs with Wilson’s
FREE copper accumulation in many tissues
How do Wilson’s patients predominately present
Central Nervous System Issues
- behavioral changes
- school performance and handwriting deteriorates
- resting and intention tremors
