Wednesday, 17 November 2010

MRCP revision battle 52.2: Congential Hyperbilinrubinaemia

This battle will briefly run through 4 conditions associated with congenital hyperbilinrubinaemia....

1. Gilberts

This is the absolute classic.  Gilberts is inherted in an autosomal recessive fashion and affects 1-2% of the population.

Gilberts is due to low levels of UDP glucuronosyltransferase.
It results in a rise in unconjugated bilirubin.

Gilberts is entirely benign and many sufferers only take on a yellow tinge when they have a concurrent illness.

2. Crigler Najjar

There are 2 types of Crigler Najjar - type 1, which is autosomal recessive, and type 2, which is autosomal dominant.

It is due to there being no UDP glucuronosyltransferase
This results in a catastophic rise in unconjugated bilirubin.

Unless the sufferer has a liver transplant they are likely to die as a baby.

3. Dubin Johnson

Dubin Johnson is an autosomal recessive condition in which there is a mutation in the cMOAT transport protein resulting in a defect of hepatic excretion of bilirubin and a rise in conjugated bilirubin.

This manifests as intermittent jaundice with RUQ pain.

Tests to confirm Dubin Johnson include:
  • coproporphyrin I levels being 3-4x higher than coproporphyrin III- in normal subjects this is reversed
  • normal levels of urine coproporphyrin  but 80% being the I isomer, when normally this would be 25%
  • at postmortem: liver has black pigmentation

Happily Dubin-Johnson is a benign condition

4. Rotor syndrome

Rotor syndrome is an autosomal recessive disorder which is similar to Dubin-Johnson and is also due to a defective mechanism of excretion of conjugated bilirubin.

It is also benign.

Rotor syndrome can be differentiated from Dubin-Johnson as:
  • Dubin-Johnson has normal levels of urinary coproporphyrin while Rotor syndrome has high levels
  • liver in Dubin-Johnson has black pigmentation whereas in Rotor syndrome it is normal

Now on to metformin...