Bile acids are found in the liver. Their role is to promote the flow and excretion of bile and to assist in the absorption of intestinal fat and fat-soluble vitamins. BASD’s are known to be a group of rare metabolic disorder which is characterized by defects in the formation (synthesis) of bile acids. Bile acid synthesis is the main pathway in breaking down and eliminating cholesterol. When this function is disrupted, the accumulation of abnormal bile acids results. This causes damage to certain organ systems. Sometimes additional symptoms like progressive neurological disease may also develop. In most cases, symptoms are present at birth and in the newborn period. This disorder can be treated by replacing missing bile acids but if left untreated it could eventually progress to life-threatening complications. BASD is caused due to mutations in specific genes which are inherited as autosomal recessive traits.
The two types of bile acid synthesis disorders can be classified as primary and secondary. When a congenital deficiency in the enzymes requires for bringing about chemical reaction is present is known as primary BASD’s. Secondary disorders are disorders that are involved in the transportation of bile acids such as low gamma-GT familial intra-hepatitic cholestasis and MDR3 deficiency.
Mutations in specific genes cause bile acid synthesis disorders. The protein product may be inefficient, faulty or absent when the mutations of the gene occur. This affects the organ systems of the body. BASD’s results from the improper synthesis of bile acids such as cholic acid and chenodeoxycholic acid. Diminished production of bile causes BASD’s.
The main function of bile acids is to promote the flow of bile. Bile is a fluid that contains water and certain minerals that carry electrolytes and materials like salt, cholesterol, phospholipids, and bilirubin (orange-yellow pigmentation) which is a product of the breakdown in hemoglobin. Bile is created in the liver. Therefore a problem in the normal flow of bile results in mal-absorption of vital nutrients and also an accumulation of toxic materials in the body.
Clinical features would include jaundice, fat and fat-soluble vitamin mal-absorption and also steatorrhea. In many cases, pruritis is absent. Liver function test would show high levels of serum transaminases, conjugated hyperbilirubinemia, and normal gamma-GT.
The histology of the liver would show the inflammation, evidence of cholestasis, giant cells and different degrees of liver fibrosis. Sometimes the disorder may have an early onset of symptoms where some patients resolve jaundice or require liver transplantation at an early age. In late-onset symptoms, liver disease is not very evident and patients might suffer from fat-soluble vitamin mal-absorption, rickets or other complications like bleeding, neuroaxonal dystrophy, and blindness. Serum liver enzymes though normal would often show an increase during the progression of liver disease to fibrosis. Adolescence and children are also affected by this condition.
Bile acid synthesis disorders are characterized by the failure to produce normal bile acids and also accumulate unusual bile acids. When this condition is not diagnosed, it could result in progressive chronic liver disease or liver failure. On early recognition, there could be a remarkable response to oral bile acid therapy.
