ABCB4 and my liver
What ABCB4 does
The liver makes bile to help digest fat. Bile is harsh: its main ingredients, bile salts, work like detergent. To keep that detergent from damaging the tiny tubes that carry bile (the bile ducts), the liver adds a protective fat to it. A pump in the liver called MDR3 moves that fat into the bile. The instructions for building the pump are in a gene called ABCB4.
When the pump is weak, bile has too little of the protective fat. Over time, it irritates and scars the bile ducts and the liver around them. It can also make gallstones and sludge form inside the liver.
What my mutations do
My main change is a nonsense mutation. Partway through the instructions, at the spot for building block 1,046, it puts an early stop signal. The copy of the gene with that change can't build a complete pump. Researchers group this kind of change as class I, the type where that copy produces no working pump.
I also have a second change in ABCB4, at building block 590, on my other copy of the gene. Each change came from a different parent. The second one is listed as a variant of uncertain significance, which means there isn't enough evidence yet to say whether it weakens the pump.
One copy versus two
About 300 harmful changes in ABCB4 are known. People with two broken copies usually develop a severe liver disease in early childhood. People with one usually have milder forms that show up later, sometimes not until adulthood.
I'm somewhere in between: one copy is confirmed broken, and the other has a change nobody can rate yet. If it turns out to be harmless, I have the one-copy form. If it turns out to weaken the pump, my liver has less working pump than most people with one broken copy.
One of the later forms is liver disease in adults with no obvious cause: liver tests that stay high and slow scarring around the bile ducts. That matches my history. My liver problems were once assumed to come from ALPS. Since the genetic results, my doctors at the NIH see this mutation as the cause.
The classic lab sign of ABCB4 disease is a high GGT, an enzyme that rises when the bile ducts are under stress. Every GGT result in my records was high.
Something else in the mix
My doctors' liver specialists have also noted high pressure in the vein that carries blood to the liver, called portal hypertension, without the heavy scarring (cirrhosis) that usually causes it. That pattern has been seen in people with immune disorders, so my ALPS may be playing a part in my liver too. Two genes, and it isn't always clear where one ends and the other begins.
How it's treated
The main treatment is a medicine called ursodiol (UDCA), a milder bile acid that makes bile less harsh on the ducts. It tends to work best when the pump still has some function left, which is more often the case with one broken copy than two.
My details
- Gene: ABCB4
- Main change: c.3136C>T, p.Arg1046Ter (a nonsense mutation), confirmed pathogenic
- Second change: c.1769G>A, p.Arg590Gln, variant of uncertain significance
- Copies: one change on each copy of the gene, inherited from different parents
- Found by: genome sequencing at the NIH; results shared with me in July 2024
My liver results since 2012 are charted on the My story page.
Sources
- Sticova E, Jirsa M. "ABCB4 disease: Many faces of one gene deficiency." Annals of Hepatology 19(2):126–133, 2020. doi.org/10.1016/j.aohep.2019.09.010