Genetic Disorders affecting the GI system Flashcards
UDP Glucuronyl transferase-related disorders
Crigler-Najjar syndrome results from a deficiency of UDP-glucuronyl transferase. Type 1 results from a complete absence of the gene with sever hyperbilirubinemia that accumulates in the brain of affected newborns and that causes a form of encephalopahty called kernicterus. Therapy includes transfusinos in the immediate neonatal period, phototherapy, heme oxygenase inhibitors to reduce transient worsening of hyperbilirubinemia, oral calcium phosphate and carbonate to form complexes with bilirubin in the gut, and liver transplantation prior to the onset of brain damage and before phototherapy becomes ineffective. Type II is a benign form of this disorder resulting from a mutation that causes a partial deficiency o the gene. Gilbert syndrome is a relatively common, benign disorder resulting from the decreased activity of DUP-glucoronyl transferase.
Dubin Johnson Syndrome
caused by a defect in the canalicular mutliple organic anion transporter (cMOAT, Mrp2, ABCC2) and leads to an accumulation of conjugated (direct) bilirubin, which can no logner e exported from the hepatocytes into the bile. This is a benign condition that usually does not require treatment. However, during pregnancy or after oral contraceptives, jaundice may occur. The latter are contraindicated in these patients.
genetic disorders of heme metabolism
criglar-najjar syndrome dubin-johnson syndrome gilbert's disease porphyria cutanea tarda acute intermittent porphyria
genetic disorders of copper and iron metabolism
wilson’s disease
hemochromatosis
genetic disoders of carbohydrate metabolism
galactosemia
hereditary fructose intolerance
PEP carboxykinase deficiency
von Gierke’s disease
enzyme that converts heme to biliverdin
heme oxygenase
enzyme that converts biliverdin to bilirubin
bilirubin reductase
the conversion of heme to bilirubin occurs in what cell
the macrophage of RES
in the blood, bilirubin transiently binds what protein for transportation, failure of this binding resulting in what condition
albumin
jaundice
in the liver, bilirubin is converted to bilirubin-monoglucuronide and then to bilirubin diglucucuronide by what enzyme
UDP-glucuronyl transferase handles both these steps
insufficient or absent UDP-glucuronyl transferase is characteristic of what disease
crigler-najjar syndrome
Type 1: total absence, severe form –> brain damage kernicture
type 2: <25% UDP-Glucuronyl transferase function
gilberts disease MoA
decrease in bilirubin with phenobarbital
liver doesnt properly process bilirubin - example of nonhemolytic jaundice
UGT1A1 gene results in decreased activity of bilirubin uridine diphosphate glucuronylosyltrasnferase
dubin johnson syndrome and rotor syndrome are both a result of
impaired biliary excretion of conjugated organic anions and bilirubin
porphoryia cutanea tarda results from a deficiency in what enzyme
uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of heme
acute intermittent porphyria is caused by a deficiency in what enzyme
pophobilinogen daminase
