Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ABCB4 (MDR3), a lipid translocator, moves phosphatidylcholine from the inner to the outer leaflet of the canalicular membrane. Genetic mutations of ABCB4 lead to three distinct but related hepatobiliary diseases. Progressive familial intrahepatic cholestasis (PFIC) type 3 is a chronic cholestatic syndrome characterized by a markedly elevated gamma-glutamyltranspeptidase. Patients present with jaundice, pruritus, and hepatosplenomegaly. Periportal inflammation progresses to biliary cirrhosis and causes portal hypertension. Ursodeoxycholic acid (UDCA) normalizes liver function tests in approximately one half of treated PFIC type 3 patients. Partial responders or nonresponders eventually will require liver transplantation. Gallstone patients with ABCB4 mutations may have low phospholipid-associated cholelithiasis syndrome, characterized by cholesterol gallstones and intrahepatic microlithiasis, along with recurrent biliary symptoms, despite cholecystectomy. Patients with ABCB4 mutations also may develop intrahepatic brown pigment stones. UDCA may improve biliary symptoms even before the dissolution of stones occurs. Additional therapies such as farnesoid X receptor ligands/agonists and benzfibrates show future therapeutic promise. Intrahepatic cholestasis of pregnancy affects pregnant women with abnormal ABCB4. These women suffer from disabling pruritus and also may experience steatorrhea. Fetuses are at high risk for prematurity and stillbirths. The definitive treatment is delivery of the baby. In the interim, limited fat intake, fat-soluble vitamin supplementation, and UDCA with or without S-adenosylmethionine can provide symptomatic relief. Additional hepatobiliary diseases related to ABCB4 mutations are likely to be identified. This may result in the discovery of additional therapies for PFIC type 3, gallstones, and intrahepatic cholestasis of pregnancy.
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PMID:The Multiple Facets of ABCB4 (MDR3) Deficiency. 1822 10

Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign macrophages with haemophagocytic activity that comforting the diagnosis of a SAM according to Ravelli and HLH-2004 criteria. Griscelli syndrome (GS) was evoked on; consanguineous family, recurrent infection, very light silvery-gray color of the hair and eyebrows, Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. The molecular biology showed mutation in RAB27A gene confirming the diagnosis of a Griscelli syndrome type 2. The first-line therapy was based on the parenteral administration of high doses of corticosteroids, associated with immunosuppressive drugs, cyclosporine A and etoposide waiting for bone marrow transplantation (BMT).
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PMID:Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature. 2987 56