67. Hereditary hyperbilirubinemias

Question 1

hereditary hyperbilirubinemias - types , mode og inheritance for each

Answer 1

1. Gilbert syndrome
2. Crigler-Najjar syndrome , type I
3. Dubin–johnson syndrome
4. ROtor syndrome
   ALL AR

Question 2

gilbert syndrome - mechanism

Answer 2

mildly decreased UDP- glucuronosyltransferase conjugation and impaired bilirubin uptake

Question 3

Gilbert syndrome - frequrncy / presentation/ findings

Answer 3

• very common and no clinical consequences
• asymptomatic or mild jaundice
• increased UCB without overt hemolysis
• more increasing UCB and Jaundice in fasting, stressm infection

Question 4

Cringler - Najjal syndrome , type I - mechanism

Answer 4

Absent of UGT ( present early in life) –> die within a few years

Question 5

Cringler - Najjal syndrome , type I - findings / symptoms

Answer 5

1. jaundice
2. kernicterus
3. increased UCB

Question 6

Cringler - Najjal syndrome, type I - treatment

Answer 6

plasmapheresis and phototherapy

Question 7

Cringler - Najjal syndrome, type II ( vs type I)

Answer 7

less severe and responds to phenobarbital , which increases liver enzyme synthesis

Question 8

Dubin - Johnson syndrome - everything

Answer 8

deficiency of bilirubin canalicular transport protein ( defective excretion ) –> conjugated hyperbilirubinemia
Grossly black liver ( Benign)

Question 9

Rotor syndrome - everything

Answer 9

similaar to DUbin - johnson but milder in presentation without black liver
DUE TO : impaired hepatic uptake (?) + excretion

Question 10

Dubin - Johnson syndrome vs Rotor syndrome according to liver

Answer 10

dubin - johnson syndrome –> black

Rotor syndrome –> no black

Question 11

• A college student with no prior medical history presents with scleral icterus during final exams. What is the likely diagnosis?

Answer 11

Gilbert syndrome, likely precipitated by fasting or stress secondary to studying

Question 12

• The parents of a child with Gilbert syndrome want to know what complications to expect. What do you tell them?

Answer 12

Gilbert syndrome has no clinical consequences other than jaundice

Question 13

• A woman occasionally has jaundice instigated by stress that goes away without treatment. What is the pathogenesis of this benign condition?

Answer 13

Slightly decreased UDP-glucuronosyltransferase activity or decreased bilirubin uptake by hepatocytes (this is Gilbert syndrome)

Question 14

• Which levels are elevated in Gilbert syndrome: conjugated bilirubin, unconjugated bilirubin, or both?

Answer 14

Unconjugated bilirubin (since UDP-glucuronosyltransferase activity is decreased)

Question 15

• A 1-y/o girl has a new unconjugated hyperbilirubinemia with no laboratory indications of hemolysis. What asymptomatic condition is likely?

Answer 15

Gilbert syndrome, which can be triggered by fasting and stress in predisposed individuals

Question 16

• A newborn has defective activity of UDP-glucuronosyltransferase, usually resulting in death within a few years of birth. Diagnosis?

Answer 16

Crigler-Najjar syndrome type I

Question 17

• A 2-week-old boy is diagnosed with Crigler-Najjar syndrome type I. What do you tell the parents about the prognosis?

Answer 17

Death occurs in childhood

Question 18

• A patient has jaundice, kernicterus, and high unconjugated bilirubin levels. He dies at age 3 years. What enzyme is missing in his disease?

Answer 18

UDP-glucuronosyltransferase (the patient has Crigler-Najjar syndrome type I)

Question 19

• The parents of a jaundiced newborn are concerned that he has Crigler-Najjar syndrome. What type of bilirubinemia would rule this out?

Answer 19

Conjugated hyperbilirubinemia (as Crigler-Najjar causes impaired conjugation, leading to an unconjugated hyperbilirubinemia)

Question 20

• What is kernicterus?

Answer 20

Bilirubin deposition in the brain

Question 21

• What would a neonate with absent UDP-glucuronosyltransferase and cerebral palsy be treated with?

Answer 21

Plasmapheresis and phototherapy (this is Crigler-Najjar syndrome)

Question 22

• A baby has hyperbilirubinemia from low UDP-glucuronosyltransferase. How can a drug-enhancing liver enzyme synthesis help you prognosticate?

Answer 22

Phenobarbital enhances enzyme synthesis in Crigler-Najjar syndrome type II (less severe/a better prognosis), but has no effect for type I

Question 23

• A newborn has persistent hyperbilirubinemia despite phototherapy. What type of bilirubinemia supports a diagnosis of Dubin-Johnson syndrome?

Answer 23

Conjugated hyperbilirubinemia (Dubin-Johnson is a defect of hepatic excretion of bile)

Question 24

• What physiologic process is defective in patients with Dubin-Johnson syndrome?

Answer 24

Excretion of bilirubin from hepatocytes

Question 25

• A patient has defective excretion of direct bilirubin. Gross pathology shows a black liver. Diagnosis?

Answer 25

Dubin-Johnson syndrome, which has the characteristic black liver on gross pathology

Question 26

• You diagnose Dubin-Johnson syndrome in a neonate with conjugated hyperbilirubinemia. How do you explain the prognosis to the parents?

Answer 26

There are no clinical consequence, as this condition is benign

Question 27

• A patient has disease symptoms similar to Dubin-Johnson syndrome, but you do not find a grossly black liver. Does the prognosis change?

Answer 27

No (this is Rotor syndrome, which is a milder form of Dubin-Johnson syndrome

Question 28

• A 22-year-old new to your practice has a history of benign unconjugated hyperbilirubinemia. Which hepatic enzyme is likely affected?

Answer 28

Glucuronosyltransferase (specifically UDP-glucuronosyltransferase in the case of Gilbert syndrome)

Question 29

• Unconjugated bilirubin is formed from ____.

Answer 29

Hemoglobin

Question 30

• What cells within the liver are part of the mononuclear phagocyte system, aiding in the conversion of hemoglobin to unconjugated bilirubin?

Answer 30

Kupffer cells

Question 31

• Describe the properties of circulating bilirubin (in normal healthy individuals). What allows it to be transported through the bloodstream?

Answer 31

Circulating bilirubin is unconjugated and water-insoluble; must be bound to albumin for transport

Question 32

• To enter hepatocytes for processing, what two spaces must circulating bilirubin pass through?

Answer 32

Junctions between endothelial cells in the hepatic sinusoid, followed by the space of Disse

Question 33

• A man has a rare mutation that slightly inhibits passage of bilirubin through the space of Disse. This presents similarly to what syndrome?

Answer 33

Gilbert syndrome (can consider this to be a form of impaired bilirubin uptake)

Question 34

• Within hepatocytes, what enzyme is tasked with converting unconjugated bilirubin into conjugated bilirubin? What function does it perform?

Answer 34

UDP-glucuronosyltransferase, it conjugates the bilirubin

Question 35

• After being acted on by UDP-glucuronosyltransferase, how does bilirubin differ from a previously circulating form?

Answer 35

It is now conjugated (bilirubin diglucuronide) and is more water soluble

Question 36

• Conjugated bilirubin is secreted into what structure so that it may become a part of bile?

Answer 36

The lumen of the bile canaliculus

Question 37

• A patient has jaundice and RUQ pain. A common bile duct gallstone is detected. This most directly impairs what step of bilirubin metabolism?

Answer 37

Secretion of conjugated bilirubin into the lumen of the bile canaliculus due to obstruction/stasis