Bile synthesis disorders (NORD)

Bile acid synthesis disorders, or BASDs, are a group of rare disorders characterized by defects in the creation or synthesis of bile acids. Bile acids are molecular compounds made in the liver that have many functions including stimulation of bile flow in the liver and triggering bile to enter the intestines to facilitate absorption of fat and fat soluble vitamins.

Cholesterol is a key ingredient in making bile acids. So, when bile acids are not formed properly, the abnormal intermediate compounds produced because of a block in the bile acid production pathway, build up within the body and cause liver injury that can lead to progressive liver failure.

Due to failure to produce normal bile acids, there is often a reduced ability to take up fat soluble vitamins from food, with associated growth failure.

Most signs and symptoms of bile acid synthesis disorders begin in infancy or early childhood with some cases not recognized until adolescence or adulthood.

Because of the build-up of toxic products in the liver, patients may experience yellowing of their skin or eyes, failure to thrive and growth deficiency, as well as an enlarged liver or spleen.

Since the normal bile acids are not present in bile, people may experience diarrhea or pale colored stools. People with a BASD may also have vitamin deficiencies, due to their inability to absorb fat and fat soluble vitamins.

As a result, they experience symptoms such as vision problems due to lack of vitamin A, rickets due to vitamin D deficiency, and blood clotting problems due to lack of vitamin K.

Sometimes the lack of vitamin E or the buildup of cholesterol-like substances can result in neurological diseases which progress throughout childhood or adulthood.

Without treatment, BASDs may lead to life-threatening conditions including scar tissue formation on the liver, high blood pressure in the major vein of the liver, abdominal swelling, and eventually liver failure.

Bile synthesis is a multistep process of making bile in the liver and requires a number of different proteins or enzymes. In BASD, genetic mutations cause the liver to produce the wrong protein, produce a non-functional protein, or cease protein production completely.

The decrease in the production of one of these essential proteins for bile synthesis ultimately causes the accumulation of intermediates in the synthesis pathway that are toxic to the liver and in some circumstances, the brain.

There are several bile acid synthesis disorders, and each disorder is classified by the specific protein or enzyme that is affected.

BASDs follow autosomal recessive inheritance, so a child must inherit a mutated gene from both parents in order to be affected.