Genetics of GI Disorders Flashcards
What are the genetic disorders related to heme metabolism?
- Crigler - Najjar syndrome
- Gilbert’s Syndrome
- Dubin - Johnson Syndrome
- Rotor Syndrome
How is Crigler - Najjar syndrome inherited?
Autosomal Recessive
Crigler - Najjar syndrome affects metabolism of _____
Bilirubin
When in life does Crigler - Najjar syndrome present?
Very early in life
Describe the 2 types of Crigler - Najjar syndromes
Type 1: mutation that causes absent UGT1A1 enzyme
Type 2: mutation that causes defective or less active UGT1A1 enzyme
Crigler - Najjar syndrome is detected because the infants have high levels of what?
Unconjugated hyperbilirubinemia
How is heme supposed to break down?
Heme Biliverdin Bilirubin Bilirubin glucuronides = Excreted
Where in the pathway for heme metabolism is the enzyme UGT1A1 important?
Taking bilirubin to bilirubin glucuronides so they can be excreted - thus a mutation in that enzyme causes crazy high levels of bilirubin
What are the symptoms/signs of Crigler - Najjar syndrome?
Severe Jaundice and brain dysfunction
Kernicterus - deafness and poor mental progession
Hypotonia
Arias Syndrome
Type 2 Crigler - Najjar syndrome (less severe than Type 1)
How does one get Gilbert’s syndrome?
Hereditary
Gilbert’s syndrome is characterized by what?
Unconjugated hyperbilirubinemia
- Decrease in bilirubin uptake (mild)
Gilbert’s syndrome is associated with a defect in?
UGT1A1 gene promotor
What are the symptoms of Gilbert’s Syndrome?
LARGELY ASYMPTOMATIC
- occasional recurrent mild jaundice that can be associated with fasting, stress and alcohol
How do you test for Gilbert’s syndrome?
Rifampin test:
- Fast 12-24 hours
- Administer Rifampin
- Bilirubin levels greater than 1.9
What is the treatment for Gilbert’s syndrome?
NONE needed
What 2 syndromes are characterized by increased levels of CONJUGATED bilirubin?
Dubin - Johnson syndrome
Rotor’s Syndrome
Dubin-Johnson syndrome has mutations in what and what does it normally do?
MRP2 - transports molecules across extra/intracellular membranes
What is the main physical exam finding with Dubin-Johnson syndrome?
BLACK LIVER
Why is the liver black in Dubin-johnson syndrome?
Impaired excretion of epinephrine metabolites
How is Dubin-Johnson syndrome inherited?
Autosomal recessive
What are the urine coproporphyrin levels with Dubin-Johnson syndrome?
Normal
Dubin-Johnson syndrome has increased _______ levels due to impaired hepatic secretion of _____
Conjugated bilirubin
Bilirubin
Rotor’s syndrome has mutations in what and what does it normally do?
OATP1B1 and OATP1B3 - facilitate liver uptake of drugs
