Hepatic Steatosis in Dunnigan-Type Familial Partial Lipodystrophy

Humboldt-Universität zu Berlin, Berlín, Berlin, Germany
The American Journal of Gastroenterology (Impact Factor: 10.76). 11/2005; 100(10):2218-24. DOI: 10.1111/j.1572-0241.2005.00234.x
Source: PubMed


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.
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.
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.
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.

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    • "The disorder is also characterized by metabolic alterations, such as insulin resistance, often leading to diabetes, and severe hypertriglyceridaemia with an increased risk of acute pancreatitis [3]. In addition, atherosclerotic processes and high blood pressure can be seen in these patients, while severe liver steatosis is commonly observed [6] [7]. Although insulin resistance is a key feature in FPLD, treatment with insulin sensitizers such as metformin and thiazolidinediones has produced conflicting results. "
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    ABSTRACT: This report highlights the metabolic, endocrine and cardiovascular comorbidities in a case of familial partial lipodystrophy (FPLD), and also evaluates the efficacy and safety of metformin therapy. Mutational analysis was carried out of the LMNA gene in a teenage girl with an FPLD phenotype. Insulin resistance, sex hormones and metabolic parameters were also evaluated, and echocardiography, electrocardiography and 24-h blood pressure monitoring were also done. The patient showed atypical fat distribution, insulin resistance and hypertrophic cardiomyopathy. Physical examination revealed muscle hypertrophy with a paucity of fat in the extremities, trunk and gluteal regions, yet excess fat deposits in the face, neck and dorsal cervical region. LMNA sequencing revealed a heterozygous missense mutation (c.1543A>G) in exon 9, leading to substitution of lysine by glutamic acid at position 515 (K515E). Moderate hypertension and secondary polycystic ovary syndrome were also assessed. Treatment with metformin resulted in progressive improvement of metabolic status, while blood pressure values normalized with atenolol therapy. Very rapid and good results with no side-effects were achieved with metformin therapy for FPLD. The association of an unusual mutation in the LMNA gene was also described.
    Diabetes & Metabolism 01/2014; 40(3). DOI:10.1016/j.diabet.2013.12.008 · 3.27 Impact Factor
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    • "Patients with this rare entity, which has an estimated prevalence of 1 in 15 million individuals (1), manifest a peculiar lipodystrophy after adolescence. In addition, metabolic complications, including insulin resistance, diabetes, hypertriglyceridemia, low HDL cholesterol levels and fatty liver, are prevalent in FPLD2 patients (3, 4). Female patients also have an increased risk for developing polycystic ovary syndrome and infertility (18). "
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    ABSTRACT: We report five consecutive patients who underwent hematopoietic stem cell transplantation (HSCT) to treat leukemia or neuroblastoma early in their lives and later manifested abnormal patterns of adipose tissue distribution. Lipoatrophy was remarkable in the gluteal regions and extremities, whereas subcutaneous fat was preserved in the cheeks, neck, and abdomen. In addition, visceral fat deposition, fatty changes in the liver, and metabolic derangements such as insulin resistance and hypertriglyceridemia were evident. These features resemble Dunnigan-type familial partial lipodystrophy, which is a rare condition caused by LMNA gene mutation. These patients shared a common medical history involving HSCT, including conditioning with total body irradiation (TBI). They also received intensive chemotherapy because of multiple metastases (n = 3), relapse (n = 3), and repetitive HSCT (n = 3). We propose HSCT as a new etiology for acquired partial lipodystrophy and recommend that patients who undergo HSCT with TBI and intensive chemotherapy early in their lives must receive careful observation for the possible development of lipodystrophy and metabolic complications.
    Clinical Pediatric Endocrinology 10/2013; 22(4):53-64. DOI:10.1292/cpe.22.53
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    ABSTRACT: The laminopathies are a diverse group of conditions caused by mutations in the LMNA gene (MIM*150330). LMNA encodes the nuclear envelope proteins lamin A and lamin C by utilization of an alternative splice site in exon 10. The human LMNA gene was identified in 1986 but it was another 13 years before it was found to be the causative gene for a disease, namely Emery Dreifuss muscular dystrophy. Since then, a further eight clearly defined phenotypes have been associated with LMNA mutations. The diversity of these phenotypes is striking with features such as premature ageing, axonal neuropathy, lipodystrophy and myopathy being seen. These phenotypes and the emerging genotype/phenotype correlations are the subject of this review.
    Clinical Genetics 11/2006; 70(4):261-74. DOI:10.1111/j.1399-0004.2006.00677.x · 3.93 Impact Factor
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