title: Hepatic steatosis in Dunnigan-type familial partial lipodystrophy.
abstract: OBJECTIVE
  Characterization of familial clusters of subjects with metabolic derangements predisposing to hepatic steatosis and nonalcoholic steatohepatitis could facilitate genomic studies to identify risk factors for their development. Dunnigan-type familial partial lipodystrophy (FPLD) is an autosomal dominantly inherited disorder caused by mutations in the LMNA gene. Affected subjects have loss of subcutaneous fat from the extremities and symptoms similar to those characterizing the metabolic syndrome, including insulin resistance and dyslipidemia. The goal of this study was to determine the prevalence of steatosis in subjects with FPLD.
  
  
  METHODS
  We examined 18 subjects from six families with FPLD for mutations in LMNA and analyzed plasma lipid and serum glucose concentrations. Liver ultrasound and serum aminotransferase activities were used as indicators of steatosis or steatohepatitis. In two subjects, histological examination of hepatic tissue was performed.
  
  
  RESULTS
  All subjects had FPLD-causing mutations in LMNA. Plasma lipids were measured in 17 subjects, 16 of whom had hyperlipidemia and 14 presented with either documented insulin resistance or diabetes mellitus. Hepatic steatosis was present in 15 subjects who had ultrasound examinations and 9 of these had elevated serum aminotransferase activities. Liver biopsy confirmed steatosis in 2 subjects.
  
  
  CONCLUSIONS
  Hepatic steatosis is part of the clinical phenotype of FPLD. This familial disorder may provide a human metabolic model system to facilitate genomic and environmental studies to determine risk factors for hepatic steatosis and nonalcoholic steatohepatitis.
authors.affiliation: Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Humboldt University, Berlin, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Lüdtke
authors.forename: Janine
authors.initials: J
authors.lastname: Genschel
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauditz
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Martin
authors.initials: M
authors.lastname: Koch
authors.forename: Wolfram
authors.initials: W
authors.lastname: Wermke
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
authors.forename: Hartmut H-J
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000273:Adipose Tissue; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D003923:Diabetes Mellitus, Lipoatrophic / Q000150:complications* / Q000201:enzymology* / Q000235:genetics; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D006801:Humans; D034904:Lamin Type A; D034882:Lamins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase