Benign recurrent intrahepatic cholestasis type 1 and 2 (BRIC: Benign recurrent intrahepatic cholestasis types 1 and 2 -BRIC1 and BRIC2-) - Genes ABCB11 and ATP8B1.
Benign recurrent intrahepatic cholestasis (BRIC) is a hepatic disease characterized by episodes of hepatic dysfunction (cholestasis). During these episodes, liver cells have a reduced capacity to release bile. These episodes can last from weeks to months and time between episodes, which usually no symptoms, can vary from weeks to years.
Those affected by this disease suffer occasional episodes of involvement of the biliary secretion, with intense itching and jaundice. Other general signs and symptoms that occur during these episodes include malaise, irritability, nausea, vomiting and lack of appetite. A common feature of BRIC is reduced absorption of fat in the body, causing the presence of excess fat in faeces (steatorrhoea). However, episodes of liver dysfunction sometimes become more serious and permanent form of liver disease called progressive familial intrahepatic cholestasis - see progressive familial intrahepatic cholestasis -. Unlike progressive familial intrahepatic cholestasis, BRIC is less intense, the signs and symptoms do not worsen over time, and the disease does not cause liver failure.
Intrahepatic cholestasis benign recurrent (BRIC) is divided into two types, BRIC1 and BRIC2, based on its genetic cause. BRIC1 is due to mutations in the ATP8B1 gene while BRIC2, is due to genetic changes in ABCB11. Signs and symptoms are the same in both.
The ATP8B1 gene, located on the long arm of chromosome 18 (18q21-q22), belongs to the family of ATP (superfamily ATPase) gene. This gene encodes a protein carrier (aminophospholipid translocase I) of some fat molecules (aminophospholipids) through the cell membrane, helping to maintain a proper balance of bile acids in bile. Most mutations BRIC1 ATP8B1 gene responsible for a single amino acid change in the protein ATP8B1. These mutations probably alter only moderately, the structure or function of the protein ATP8B1. Through unknown mechanisms, mutations in the ATP8B1 gene lead to the accumulation of bile acids in the liver cells, causing the signs and symptoms of BRIC1. However, it is unclear what causes episodes begin or end. Sometimes, people with BRIC1 have been diagnosed later with progressive familial intrahepatic cholestasis.
The ABCB11 gene (ATP-binding cassette, subfamily B-MDR / TAP, member 11), located on the long arm of chromosome 2 (2q24), belongs to the family of ABC genes (ATP-Binding tranporters cassette), and the family ATP (superfamily ATPase) gene. This gene encodes a bile salt export protein (BSEP: Bile Salt Export Pump) that moves bile salts of hepatocytes. Mutations in the gene BRIC2 responsible ABCB11, causing a reduction of 40 to 50% of bile salt transport. The subsequent accumulation of bile salts in the liver results in the signs and symptoms of BRIC2. However, it is unclear what causes episodes begin or end. ABCB11 gene mutations have also been linked with progressive familial intrahepatic cholestasis - see progressive familial intrahepatic cholestasis -.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. BRIC some people with no family history of the disease. These cases are due to mutations in the ATP8B1 gene or ABCB11 occur in body cells after conception and not inherited.
Tests in IVAMI: in IVAMI perform detection of mutations associated with benign recurrent intrahepatic cholestasis (BRIC), by complete PCR amplification of the exons of the ATP8B1 and ABCB11, respectively, and subsequent sequencing genes.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).