Autosomal recessive polycystic kidney disease (ARPKD) is caused by a genetic mutation in the gene, PKHD1.
PKHD1 is a gene which codes for a protein called fibrocystin found in cells of kidneys, liver, lungs and pancreas. Fibrocystin is protein, which is located on a specialised part of the cell called the cilia, the sensing device of the cell.
A healthy kidney contains a large number of ducts (channels), which absorb some of the fluids that pass through the kidney. Due to the genetic mutation in PKHD1, some of the ducts begin to pass out fluid instead of absorbing it, and this leads to cyst formation. Scars are also formed and, together with cysts, the normal structure of the kidneys are destroyed, leading to high blood pressure and kidney failure.
The PKHD1 mutation sometimes has a similar effect on the bile duct. The bile duct helps to move bile from the liver into the gallbladder, a small pouch that stores bile when it is not being used. Bile is a fluid that the digestive system uses to help break down fats. The bile is then passed from the gallbladder into the small intestine.
The PKHD1 mutation causes the bile ducts to become enlarged. This makes the child with ARPKD more prone to an infection called cholangitis, which can be very serious. Another problem is blood flow through the liver, leading to portal hypertension. This causes enlargement of the spleen and enlargement of vessels in stomach lining, causing varices. Varices can be treated with sclerotherapy or by banding, but this does not treat the initial problem with the liver. A liver transplant may be necessary if there is significant portal hypertension or repeated bouts of cholangitis.
Autosomal recessive mutation
All the genes in your body come in pairs. You receive one half of the pair from your mother and the other half from your father.
The mutation that causes ARPKD is an autosomal recessive mutation. This means that you need to receive two copies of the mutated gene in order to develop the condition – one from your mother and one from your father.
If you only receive one copy of the mutated gene from one of your parents, you will not develop ARPKD but you will carry the mutated gene. It is estimated that one in 70 people in England is a carrier of the mutated gene.
If you are a carrier of the mutated gene and you conceive a baby with a partner who is also a carrier, there is:
- a one in four chance that the baby will receive a pair of normal genes
- a one in two chance that the baby will receive one normal gene and one mutated gene, and become a carrier of the PKHD1 mutation
- a one in four chance that the baby will receive a pair of mutated genes and develop ARPKD
