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...
