Hepatic steatosis in Dunnigan-type familial partial lipodystrophy.
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.
Lüdtke
Angelika
A
Department of Gastroenterology, Hepatology & Endocrinology, Charité, Campus Mitte, Humboldt University, Berlin, Germany.
Genschel
Janine
J
Brabant
Georg
G
Bauditz
Jürgen
J
Taupitz
Matthias
M
Koch
Martin
M
Wermke
Wolfram
W
Worman
Howard J
HJ
Schmidt
Hartmut H-J
HH
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*
C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase