Low phospholipid associated cholelithiasis
Low phospholipid associated cholelithiasis (LPAC) is a disease of the biliary tract that is associated with the increased formation of gallstones .
Pathogenesis
In LPAC, mutations in the MDR3 / ABCB4 gene (7q21.1) are to be regarded as the cause. Therefore, there is often a familial accumulation among those affected. These mutations lead to the phospholipid secretion in the bile being reduced, which in turn means that more gallstones are formed due to the oversaturation with cholesterol. Bile salts also damage the membrane of the biliary tract due to their cytotoxic effect.
Symptoms
The most common first manifestation of the disease occurs in adulthood and occurs predominantly in young patients under 40 years of age who experience recurrent symptoms from cholelithiasis . Usually a first degree relative is already affected by this disease. If patients with symptomatic cholelithiasis meet at least two of the three criteria with 1.) age of onset under 40 years, 2.) cholelithiasis despite a cholecystectomy and 3.) sonographic evidence of sludge and micro-concretions in the biliary tract, the suspicion of LPAC is likely and requires further clarification.
Patients present with complaints of cholecystolithiasis or choledocholithiasis . This typically manifests itself with colicky upper abdominal pain, vomiting, jaundice or also fever and sepsis in the case of further exacerbation of cholangitis . Even after a cholecystectomy , symptoms often reappear, caused by the irritation and inflammation of the bile ducts due to new stone formation. In up to half of all cases, women during pregnancy develop intrahepatic cholestasis with pruritus, jaundice and increased bile salts as a complication .
Diagnosis
Using sonography , computed tomography or magnetic resonance tomography , stone formation and the cholestasis triggered by the damage to the bile duct can be visualized . In laboratory tests, LPAC is primarily noticeable as an increase in γ-glutamyltransferase and bile salts . Genetic testing for the affected mutations of MDR3 or ABCB4 should be carried out by a special gastroenterological laboratory.
therapy
Patients should take oral ursodeoxycholic acid (about 10–15 mg / kg body weight / day) for life . This also applies regardless of whether a typical ABCB4 mutation is detected. In addition, any hypercholesterolemia should be treated with statins , as fibrates can promote the formation of gallstones. Specific therapies that act directly on the affected mutations are currently under development.
Individual evidence
- ↑ a b c https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=DE&data_id=10932&MISSING%20CONTENT=Low-phospholipid-associated-cholelithiasis&search=Disease_Search_Simple&title=Low-assocolipid oriated or .net - portal for rare diseases
- ↑ a b c https://www.uniklinik-duesseldorf.de/patienten-besucher/klinikeninstitutezentren/klinik-fuer-gastroenterologie-hepatologie-und-infektiologie/klinik/fuer-patienten/diagnostische-und-therapeutische-verfahren/zentrum- for-congenital-liver-diseases-cholestasis-laboratory / analysis-coding-exons / lpac University Hospital Düsseldorf
- ↑ a b https://www.drfalkpharma.de/uploads/tx_toccme2/FGK_3_19_Keitel_Web.pdf Genetic causes of cholestatic liver diseases