67. Hereditary hyperbilirubinemias Flashcards
hereditary hyperbilirubinemias - types , mode og inheritance for each
- Gilbert syndrome
- Crigler-Najjar syndrome , type I
- Dubin–johnson syndrome
- ROtor syndrome
ALL AR
gilbert syndrome - mechanism
mildly decreased UDP- glucuronosyltransferase conjugation and impaired bilirubin uptake
Gilbert syndrome - frequrncy / presentation/ findings
- very common and no clinical consequences
- asymptomatic or mild jaundice
- increased UCB without overt hemolysis
- more increasing UCB and Jaundice in fasting, stressm infection
Cringler - Najjal syndrome , type I - mechanism
Absent of UGT ( present early in life) –> die within a few years
Cringler - Najjal syndrome , type I - findings / symptoms
- jaundice
- kernicterus
- increased UCB
Cringler - Najjal syndrome, type I - treatment
plasmapheresis and phototherapy
Cringler - Najjal syndrome, type II ( vs type I)
less severe and responds to phenobarbital , which increases liver enzyme synthesis
Dubin - Johnson syndrome - everything
deficiency of bilirubin canalicular transport protein ( defective excretion ) –> conjugated hyperbilirubinemia
Grossly black liver ( Benign)
Rotor syndrome - everything
similaar to DUbin - johnson but milder in presentation without black liver
DUE TO : impaired hepatic uptake (?) + excretion
Dubin - Johnson syndrome vs Rotor syndrome according to liver
dubin - johnson syndrome –> black
Rotor syndrome –> no black
• A college student with no prior medical history presents with scleral icterus during final exams. What is the likely diagnosis?
Gilbert syndrome, likely precipitated by fasting or stress secondary to studying
• The parents of a child with Gilbert syndrome want to know what complications to expect. What do you tell them?
Gilbert syndrome has no clinical consequences other than jaundice
• A woman occasionally has jaundice instigated by stress that goes away without treatment. What is the pathogenesis of this benign condition?
Slightly decreased UDP-glucuronosyltransferase activity or decreased bilirubin uptake by hepatocytes (this is Gilbert syndrome)
• Which levels are elevated in Gilbert syndrome: conjugated bilirubin, unconjugated bilirubin, or both?
Unconjugated bilirubin (since UDP-glucuronosyltransferase activity is decreased)
• A 1-y/o girl has a new unconjugated hyperbilirubinemia with no laboratory indications of hemolysis. What asymptomatic condition is likely?
Gilbert syndrome, which can be triggered by fasting and stress in predisposed individuals
• A newborn has defective activity of UDP-glucuronosyltransferase, usually resulting in death within a few years of birth. Diagnosis?
Crigler-Najjar syndrome type I
• A 2-week-old boy is diagnosed with Crigler-Najjar syndrome type I. What do you tell the parents about the prognosis?
Death occurs in childhood
• A patient has jaundice, kernicterus, and high unconjugated bilirubin levels. He dies at age 3 years. What enzyme is missing in his disease?
UDP-glucuronosyltransferase (the patient has Crigler-Najjar syndrome type I)
• The parents of a jaundiced newborn are concerned that he has Crigler-Najjar syndrome. What type of bilirubinemia would rule this out?
Conjugated hyperbilirubinemia (as Crigler-Najjar causes impaired conjugation, leading to an unconjugated hyperbilirubinemia)
• What is kernicterus?
Bilirubin deposition in the brain
• What would a neonate with absent UDP-glucuronosyltransferase and cerebral palsy be treated with?
Plasmapheresis and phototherapy (this is Crigler-Najjar syndrome)
• A baby has hyperbilirubinemia from low UDP-glucuronosyltransferase. How can a drug-enhancing liver enzyme synthesis help you prognosticate?
Phenobarbital enhances enzyme synthesis in Crigler-Najjar syndrome type II (less severe/a better prognosis), but has no effect for type I
• A newborn has persistent hyperbilirubinemia despite phototherapy. What type of bilirubinemia supports a diagnosis of Dubin-Johnson syndrome?
Conjugated hyperbilirubinemia (Dubin-Johnson is a defect of hepatic excretion of bile)
• What physiologic process is defective in patients with Dubin-Johnson syndrome?
Excretion of bilirubin from hepatocytes
• A patient has defective excretion of direct bilirubin. Gross pathology shows a black liver. Diagnosis?
Dubin-Johnson syndrome, which has the characteristic black liver on gross pathology
• You diagnose Dubin-Johnson syndrome in a neonate with conjugated hyperbilirubinemia. How do you explain the prognosis to the parents?
There are no clinical consequence, as this condition is benign
• A patient has disease symptoms similar to Dubin-Johnson syndrome, but you do not find a grossly black liver. Does the prognosis change?
No (this is Rotor syndrome, which is a milder form of Dubin-Johnson syndrome
• A 22-year-old new to your practice has a history of benign unconjugated hyperbilirubinemia. Which hepatic enzyme is likely affected?
Glucuronosyltransferase (specifically UDP-glucuronosyltransferase in the case of Gilbert syndrome)
• Unconjugated bilirubin is formed from ____.
Hemoglobin
• What cells within the liver are part of the mononuclear phagocyte system, aiding in the conversion of hemoglobin to unconjugated bilirubin?
Kupffer cells
• Describe the properties of circulating bilirubin (in normal healthy individuals). What allows it to be transported through the bloodstream?
Circulating bilirubin is unconjugated and water-insoluble; must be bound to albumin for transport
• To enter hepatocytes for processing, what two spaces must circulating bilirubin pass through?
Junctions between endothelial cells in the hepatic sinusoid, followed by the space of Disse
• A man has a rare mutation that slightly inhibits passage of bilirubin through the space of Disse. This presents similarly to what syndrome?
Gilbert syndrome (can consider this to be a form of impaired bilirubin uptake)
• Within hepatocytes, what enzyme is tasked with converting unconjugated bilirubin into conjugated bilirubin? What function does it perform?
UDP-glucuronosyltransferase, it conjugates the bilirubin
• After being acted on by UDP-glucuronosyltransferase, how does bilirubin differ from a previously circulating form?
It is now conjugated (bilirubin diglucuronide) and is more water soluble
• Conjugated bilirubin is secreted into what structure so that it may become a part of bile?
The lumen of the bile canaliculus
• A patient has jaundice and RUQ pain. A common bile duct gallstone is detected. This most directly impairs what step of bilirubin metabolism?
Secretion of conjugated bilirubin into the lumen of the bile canaliculus due to obstruction/stasis
