The Genetics of GI Disorders Flashcards
what are the genetic disorders related to heme-metabolism?
crigler-Najjar Syndrome, gilbert’s disease, dubin-johnson syndrome, rotor syndrome
what is crigler najjar syndrome?
rare autosomal recessive disorder that affects the metabolism of bilirubin; hereditary unconjugated hyperbilirubinemia
what does crigler najjar syndrome cause?
non-hemolytic jaundice, higher than normal levels of unconjugated bilirubin, and brain damage in infants
what would you expect to find in an infant with crigler najjar syndrome?
absent or very low levels of hepatic bilirubin-glucose
what are the two types of crigler najjar syndrome?
type I: severe jaundice and kernicterus and Type II: less severe
type I crigler najjar syndrome is caused by a mutation in what?
UGT1A1- it renders the enzyme activity totally absent or not expressed
type II crigler najjar syndrome is caused by a mutation where?
in UGT1A1 coding region- renders the enzyme defective and less active than normal
how does crigler najjar patient present?
neonatal jaundice, sepsis, hypotonia, kernicterus, occulomotor palsy
what is kernicterus caused by?
bilirubin deposition in the brain
what can you use to treat type II crigler najjar?
phenobarbital-UGT1A1 inducer
what is gilbert’s syndrome?
hereditary unconjugated hyperbilirubinemia due to a defect in the gene promoter for UGT1A1
what happens in gilbert’s syndrome?
there is a mild decrease in UDP-glucuronyl transferase activity due to lower expression of wild type enzyme; mild decrease in bilirubin uptake
how does a patient with gilbert’s syndrome present?
mild jaundice, associated with fasting; stress; EtOH
how would you diagnose gilbert’s syndrome?
if there was isolated unconjugated hyperbilirubinemia without evidence of hepatitis or hemolysis
what is the treatment for gilbert’s syndrome?
no treatment needed; avoid certain medications though- like irinotecan
what is Dubin-Johnson Syndrome caused by?
a mutation in MRP2
what is rotor’s syndrome caused by?
mutations in OATP1B1 and OATP1B3
what is Dubin-Johnson syndrome?
hereditary conjugated hyperbilirubinemia (decreased hepatic excretion of conjugated bilirubin)
what causes the grossly black liver in Dubin Johnson Syndrome?
it is due to impaired excretion of epinephrine metabolites
what is the milder form of Dubin Johnson syndrome that does not cause the grossly black liver?
Rotor’s syndrome
In a patient with rotor’s syndrome, what do their total urine coproporphyrin levels look like?
they are elevated
in a patient with Dubin-Johnson syndrome, what do their total urine coproporphyrin levels look like?
they are normal
what is wilson’s disease caused by?
a mutation in the ATP7B gene
what does the mutation in the ATP7B gene cause?
inadequate copper excretion by the liver into bile; failure of copper to enter circulation bound to ceruloplasmin
what does a patient with wilson’s disease typically present with?
parkinson-like symptoms (secondary to the copper deposits in putamen) like hemiballisumus and dementia
what are the physical exam findings of a patient with wilson’s disease?
cirrhosis and kayser-fleischer rings (corneal deposits)
what do the labs look like in a patient with wilson’s disease?
decrease total serum copper due to decrease ceruloplasmin, increased serum non-cerulopasmin bound copper, increased urine/serum free copper, and hemolytic anemia
what is a patient with wilson’s disease at risk of?
hepatitis, cirrhosis, and hepatocellular carcinoma
what is a specific test used for Gilbert’s syndrome?
Rifampin test
