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
what is an AR inherited disorder that causes iron toxicity in the body from unregulated duodenal absorption because of low hepciderin levels and causes liver damage, diabetes, heart failure, and bronzed skin
hemochromatosis
describe the relationship between macrophages and iron
MO’s engulf and destroy RBCs and causes the extraction of iron from Hg.
- allows iron binding to transferrin for safe travel throughout the body
