GI Genetic disorders Flashcards
what is the function of MRP2 and OATP in intestinal epilthelial cells and hepatocytes
MRP2
- IC: bring molecules from blood into intestine
- hepatocyte: bring molecules from hepatocyte into bile canaliculi
OATP
- IC: brings molecules from intestine to the blood
- hepatocyte: Brings molecules from blood into the hepatocyte (like ASBT)
describe Crigler Najjar syndrome and its mode of genetic inheritance
- autosomal recessive
- mutated UGT1A1
- unconjugated hyperbilirubinemia
- Type 1 (severe) Type 2 (less severe)
- symptoms: jaundice, sepsis, possible kernicterus, oculomotor palsy
- tx: phenobarbital (type 2), liver transplant (type 1), phototherapy, plasmapheresis
- AVOID IRINOTECAN anti-cancer drug excreted by UGT1A1
- no yellow eyes
describe Gilberts syndrome and its mode of genetic inheritance
- autosomal recessive or dominant (pretty common)
- defect in gene PROMOTER for UGT1A1
- causes mild decreases in UGT1A1 activity so indirect hyperbilirubinemia
- most common cause of isolated UB with normal LFTs
- usually no symptoms unless alcohol, stress, or fasting
- dx: fasting test (specific), rifampin test (less specific), both increase levels of UB
- tx: usually no tx; but AVOID IRINOTECAN anti-cancer drug
describe Dubin Johnson syndrome and its mode of genetic inheritance
- autosomal recessive
- mutation of MRP2
- causes black liver and direct hyperbilirubinemia; and total increase in bilirubin
- benign condition
- *normal urine coproporhyrin levels
describe Rotor syndrome and its mode of genetic inheritance
- autosomal recessive
- mutation of OATP1B1 and OATP1B3 (specific to bring in from blood to hepatocytes)
- NO black liver, but Direct hyperbilirubinemia and bilirubinuria (in urine) is common
- benign condition, possible jaundice (esp with birth control)
**elevated urine coproporhyrin levels
what causes jaundice at 2-6 weeks of age, elevated conjugated hyperbilirubinemia, jaundice, dark urine, and clay (acholic) colored stool
congenital biliary atresia
which disease usually presents with anemia and a positive COOMBs test in mother and infant
isoimmune hemolytic disease
when do you see breast milk jaundice occur? breast feeding jaundice?
breast milk jaundice
- in second week of life (after day 7)
- elevated UB
- unknown cause
breast feeding jaundice
- in 2-4 days of life
- jaundice from insufficient intake of breast milk
describe Wilsons disease (aka hepatolenticular degeneration) and its mode of genetic inheritance
- autosomal recessive
- mutation in ATP7B (which binds copper to transporter ceruloplasmin and/or packages cooper into vesicles for exocytosis to bile)
- causes elevated free copper which generates free radicals and tissue damage and hemolytic anemia (decreased total serum copper, decreased creuloplasmin, increased free copper, urine copper, and apoceruloplasmin)
- affects liver, brain, cornea, joints
- symptpms: CNS problems (parkinson’s life symptoms, spastic movement, dementia), cirrhosis, and KAYSER-FLEISCHER RINGS (multicolored rings around cornea)
- use chelating agent for excretion (penicillamine) or zinc
- *cooper and zinc compete for absorption
- *increases risk of hepatitis, cirrhosis, and liver cancer
describe galactosemia and its mode of genetic inheritance
- *autorecessive
1. classic - mutation in GALT causes absent galactose-1-phosphate transferase enzyme which makes glucose-1-phosphate
- elevated G1P is toxic and causes infantile cataracts, brain damage, failure to thrive, jaundice, and hepatomegaly
tx: eliminate galactose and lactose from diet
- type 2 = galactokinase def - infant cataracts
- type 3 = epimerase def (GALE mutation) - spleen and liver problems
describe hereditary fructose intolerance and its mode of genetic inheritance
- autorecessive
- aldolase B deficiency causes defect in fructose metabolism
- elevated fructose-1-phosphate
- toxic to liver, kidneys, and SI and causes stops glycolysis
- symtpms: hypoglycemia
- symtpms only occur if ingest fructose, sucrose, or sorbitol so eliminate from diet
describe fructokinase deficiency and its mode of genetic inheritance
- autorecessive
- hepatic fructokinase deficiency
- elevated fructose in blood
- causes fructosuria (fructose in urine) in variable amounts depending on diet
- fructose is either excreted in urine or becomes F6P
describe Von Gierkes disease (glycogen storage disease 1a) and type 1b and their mode of genetic inheritance
- autorecessive
1. 1a - def of G-6-Phosphatase enzyme which frees glucose in glucose metabolism of glycogen
- symp: fasting hypoglycemia, hepatomegaly, lactic acidosis, elevated triglycerides
- 1b
- defect transporter protein for G6P to get from cytosol to lumen
- decrease in available free glucose from glycogen
- same symptpms as above
*can treat with cornstarch at night
describe PEPCK deficiency and its mode of genetic inheritance
- autorecessive
- gluconeogenesis disorder
- def in PEPCK which converts OAA–> PEP
- elevated OAA causes acidemia, hypoglycemia, hepatomegaly, loss of muscle tone
- causes PEP production in the mitochondria
describe PEP production in the mitochondria
- OAA is converted to PEP in the mitochondria by mitochondrial PEPCK
- occurs when lactate levels are high bc lactate prevents OAA conversion in the cytosol where it normally occurs
