Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polycystic liver diseases (PCLDs) are a heterogeneous group of genetic disorders characterized by the development of multiple fluid-filled cysts in the liver, which derive from cholangiocytes, the epithelial cells lining the bile ducts. When these cysts grow, symptoms such as abdominal distension, nausea, and abdominal pain may occur. PCLDs may exist isolated (i.e., autosomal dominant polycystic liver disease, ADPLD) or in combination with renal cystogenesis (i.e., autosomal dominant polycystic kidney disease and autosomal recessive polycystic liver disease). The exact prevalence of PCLDs is unknown, but is estimated to occur in approximately 1:1000 persons. Although the pathogenesis of each form of PCLD appears to be different, increasing evidences indicate that hepatic cystogenesis is a phenomenon that may involve somatic loss of heterozygosity (LOH) in those pathological conditions inherited in a dominant form. A recent report, using highly sophisticated methodology, demonstrated that ADPLD patients with a germline mutation in the protein kinase C substrate 80K-H (PRKCSH) gene mostly develop hepatic cystogenesis through a second somatic mutation. While hepatocystin, the PRKCSH-encoding protein, was absent in the hepatic cysts with LOH, it was still expressed in the heterozygous cysts. On the other hand, no additional trans-heterozygous mutations on the SEC63 homolog (S. cerevisiae/SEC63) gene (also involved in the development of PCLDs) were observed. These data indicate that PCLD is recessive at the cellular level, and point out the important role of hepatocystin loss in cystogenesis. In this commentary, we discuss the knowledge regarding the role of somatic second-hit mutations in the development of PCLDs, and the most relevant findings have been highlighted.
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PMID:Somatic second-hit mutations leads to polycystic liver diseases. 2332 78

Polycystic liver disease (PLD) is the result of embryonic ductal plate malformation of the intrahepatic biliary tree. The phenotype consists of numerous cysts spread throughout the liver parenchyma. Cystic bile duct malformations originating from the peripheral biliary tree are called Von Meyenburg complexes (VMC). In these patients embryonic remnants develop into small hepatic cysts and usually remain silent during life. Symptomatic PLD occurs mainly in the context of isolated polycystic liver disease (PCLD) and autosomal dominant polycystic kidney disease (ADPKD). In advanced stages, PCLD and ADPKD patients have massively enlarged livers which cause a spectrum of clinical features and complications. Major complaints include abdominal pain, abdominal distension and atypical symptoms because of voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ. Renal failure due to polycystic kidneys and non-renal extra-hepatic features are common in ADPKD in contrast to VMC and PCLD. In general, liver function remains prolonged preserved in PLD. Ultrasonography is the first instrument to assess liver phenotype. Indeed, PCLD and ADPKD diagnostic criteria rely on detection of hepatorenal cystogenesis, and secondly a positive family history compatible with an autosomal dominant inheritance pattern. Ambiguous imaging or screening may be assisted by genetic counseling and molecular diagnostics. Screening mutations of the genes causing PCLD (PRKCSH and SEC63) or ADPKD (PKD1 and PKD2) confirm the clinical diagnosis. Genetic studies showed that accumulation of somatic hits in cyst epithelium determine the rate-limiting step for cyst formation. Management of adult PLD is based on liver phenotype, severity of clinical features and quality of life. Conservative treatment is recommended for the majority of PLD patients. The primary aim is to halt cyst growth to allow abdominal decompression and ameliorate symptoms. Invasive procedures are required in a selective patient group with advanced PCLD, ADPKD or liver failure. Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction.
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PMID:Polycystic liver disease: an overview of pathogenesis, clinical manifestations and management. 2488 61