Genetics of GI Disorders Flashcards
Describe Crigler Najjar
Autosomal recessive
Affects metabolism of bilirubin
Causes jaundice due to high levels of unconjugated bilirubin
Can also cause brain damage in infants
What is type I vs a type II UGT1A1 mutation in Criggler Najjar Syndrome?
Type I: Enyzme activity is totally absent or not expressed
Type 2: Enzyme is defective and less active than normal
What medication is only given to type II patients with Crigler Najjar?
Phenobarbital-UGT1A1 inducer
What is Gilberts Syndrome?
Defect in gene promotor for UGT1A1
Mildly low UDP-glucuronyl transferase activity due to lower expression of wild type enzyme
Mildly low bilirubin uptake
AR or AD inheritance
What are some Gilbert’s Syndrome Symptoms?
Mild Jaundice
Associated with fasting
stress; infection
ETOH intake
What is a way to diagnose Gilberts?
Fasting test- Unconjugated bilirubin will rise
Rifampin test- Unconjugated bilirubin rises
What is Dubin-Johnson/Rotor’s Syndrome?
Hereditary conjugated hyperbilirubinemia
Dubin Johnson- Mutation in MRP2 (Black liver)
Rotor’s Syndrome- Mutation in OATP1B1
Both have low hepatic excretion of conjugated bilirubin
AR inheritance
What transporter proteins have mutations in Rotor’s Syndrome?
OATP1B1
OATP1B3
What do urine coproporphyrin levels look like in Dubin-Johnson/Rotor’s Syndrome?
Elevated in Rotor’s
Normal in DJS
What is Wilson’s Disease?
Free copper accumulation in the tissues
Mutation in ATP7B results in inadequate copper excretion by liver into bile
failure of copper to enter circulation bound to cerulopasmin
AR inheritance
What are some symptoms of Wilson’s Disease?
Parkinson-like symptoms
Hemiballismus-flailing, ballistic, undesired movements
Dementia
Cirrhosis
Multicolored with concentric rings around the periphery
What are lab findings in a patient with Wilson’s Disease?
Low serum copper due to low cerulopasmin
Increased serum non-ceruloplasmin bound copper
Increase urine/serum free copper
Hemolytic anemia
How can you treat Wilson’s Disease?
Ammonium tetrathiomolybdate–> facilitates urinary excretion of copper
Penicillamine and trientine –> copper chelating agent
Zinc –> Competes with copper for absobtion in the gut via the same transport (ATPB7)
What are some possible risk factors of having wilson’s disease?
Risk factor for
hepatitis, cirrhosis, and hepatocellular carcinoma
What would someone with Wilson’s Disease labs look like?
Low total serum copper
Increased serum non-cerulopasmin bound copper
Increased urine/serum free copper
hemolytic anemia
Liver biopsy: If performed will show increased hepatic copper
