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Barraquer-Simons lipodystrophy is a rare disorder of unknown origin characterized by a progressive atrophy of the subcutaneous fat of the upper part of the body. Renal disease with abnormalities of complement factors is the most frequent accompanying feature. A case is presented in which bilateral facial contour has been restored simultaneously with two deepithelialized TRAM flaps.
We report on a mentally retarded girl with dysmorphic facies (hypertelorism, upslanting palpebral fissures, blepharophimosis, prominent teeth), who suffered from juvenile-onset insulinopenic diabetes mellitus and lipodystrophy. She could represent an undescribed MCA/MR syndrome.
We present a case-report and review of the literature on membranous lipodystrophy. This is a rare disease characterized by progressive presenile dementia, multiple bone cysts with pathologic fractures, generalized cerebral seizures with abnormal EEG and bilateral calcifications of the basal ganglia. Neuropathological findings are neuroaxonal dystrophy with neurofilaments in the axons, neuronal cell loss and fibrillary gliosis. The disease is usually inherited as an autosomal recessive. The pathogenesis is unknown but is believed to be an enzyme defect of the glycolipid metabolism.
Progressive partial lipodystrophy (PPL) was diagnosed in two girls aged 6 and 8 years. PPL is characterized by loss of subcutaneous fat, starting in the face and progressing to trunk and arms. Diagnosis is based upon the cachectic appearance and the normal growth parameters. It is a rare disease of unknown aetiology, usually beginning in childhood and more frequent in females. An association with diabetes mellitus, hypertriglyceridaemia and glomerulonephritis has been described. Follow-up should be focused on these and on psychological effects. No causal therapy is available. The facial appearance can be restored by injection of liquid silicones. Life expectancy does not appear to be affected.
The case of a child who developed partial lipodystrophy and metabolic abnormalities during treatment of juvenile dermatomyositis is described and discussed.
Membranous lipodystrophy apparently is a new disease, first reported and named by Nasu and associates 31 in 1971. We have collected six cases of this disease. The initial manifestation was articular pain at adolescence. Symmetrical changes in the bones of the extremities then appeared and the disease seemed to progress slowly with age. The younger patients exhibited only skeletal pain or fractures, while the older patients had some neuropsychiatric changes. Three of the patients died in middle age. The cystic bone lesions contained a yellow, lipid-like substance which histologically showed a characteristic membranocystic appearance. Electron microscopic study showed unique features, but biochemical analysis of the substance did not reveal a definable abnormality.
INTRODUCTION: Low-molecular weight heparin-induced cutaneous necrosis is exceptional. Pathogenesis remains unclear. We report an exceptional case with elective localization of the necrotic areas in insulin lipodystrophic tissue. CASE REPORT: A 69-year old patient developed areas of skin necrosis after starting enoxaparin therapy. These areas were located far from the points of injection and focalized on skin areas where the patient had been injecting insulin daily for the last four years. These areas had an aspect of insulin lipodystrophy. Biopsy specimens showed leukocytoclastic vasculitis. There were no associated biological anomalies. One month later, prick-tests were made with different low-molecular weight heparins and calcium heparinate in a lipodystrophic area together with an enoxaparin control test in healthy skin. The only positive test was for enoxaparin in an insulin lipodystrophic area (hard erythema at 24 hours). Histology at 72 hours demonstrated leukocytoclastic vasculitis. DISCUSSION: Six cases of cutaneous necrosis induced by low-molecular weight heparin have been reported, including three cases with enoxaparin. Two pathophysiological mechanisms could be involved: (i) localized heparin-dependent platelet aggregation, or (ii) vasculitis induced by type III hypersensitivity reaction. In our case, the leukocytoclastic aspect of the vasculitis was compatible with an immune complex hypersensitivity reaction. The localization of the necrotic areas would be explained by enoxaparin-induced preferential deposit of immune complexes in the vascular turbulences present in lipodystrophic areas.
An autopsy case of Nasu-Hakola's disease (membranous lipodystrophy) was reported. A 29-year-old Japanese woman whose younger sister had been affected with typical Nasu-Hakola's disease with skeletal and neuropsychiatric syndromes and membrano-cystic lesions in the bones developed forgetfulness and lack of initiative. The clinical features were characterized by diminished drive, apathy, euphoria, disturbance of attention, amnestic syndrome, and gait disturbance. The clinical course of her illness was 8 years. The neuropathologic examination revealed marked symmetrical gliosis of the cerebral white matter (sclerosing leukodystrophy) predominantly in the frontal and temporal lobes with slight or moderate demyelination (dissociation glio-myelinique) and widespread axonal changes such as fragmentation and spheroid in the white matter of the cerebral hemisphere, cerebellum, basal ganglia, and brain stem. The ultrastructure of spheroids showed neurofilamentous accumulation. We discussed the importance of axonal changes with regard to the pathogenesis and etiogenesis of the disease.
AIMS/HYPOTHESIS: Familial partial lipodystrophy (FPLD) and obesity are both associated with increased risks of type 2 diabetes and cardiovascular disease. Although adipokines have been implicated, few data exist in subjects with FPLD; therefore we investigated a family with FPLD due to a lamin A/C mutation in order to determine how abnormalities of the plasma adipokine profile relate to insulin resistance and the metabolic syndrome. METHODS: Plasma levels of adiponectin, leptin, resistin, IL-1beta, IL-6 and TNF-alpha in 30 subjects (ten patients, 20 controls) were correlated with indices of metabolic syndrome. RESULTS: Compared with controls, FPLD patients had significantly lower plasma levels of adiponectin (3.7+/-1.0 in FDLP cases vs 7.1+/-0.72 mug/ml in controls, p=0.02), leptin (1.23+/-0.4 vs 9.0+/-1.3 ng/ml, p=0.002) and IL-6 (0.59+/-0.12 vs 1.04+/-0.17 pg/ml, p=0.047) and elevated TNF-alpha (34.8+/-8.1 vs 13.7+/-2.7 pg/ml, p=0.028), whereas IL-1beta and resistin were unchanged. In both groups, adiponectin levels were inversely correlated with body fat mass (controls, r=-0.44, p=0.036; FDLP, r=-0.67, p=0.025), insulin resistance (controls, r=-0.62, p=0.003; FDLP, r=-0.70, p=0.025) and other features of the metabolic syndrome. TNF-alpha concentrations were positively related to fat mass (controls, r=0.68, p=0.001; FDLP, r=0.64, p=0.048) and insulin resistance (controls, r=0.86, p=0.001; FDLP, r=0.75, p=0.013). IL-6, IL-1beta and resistin did not demonstrate any correlations with the metabolic syndrome in either group. CONCLUSIONS/INTERPRETATION: Low adiponectin and leptin and high TNF-alpha were identified as the major plasma adipokine abnormalities in FPLD, consistent with the hypothesis that low adiponectin and high TNF-alpha production may be mechanistically related, and perhaps responsible for the development of insulin resistance and cardiovascular disease in FPLD.
The Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is characterized by a near-total congenital absence of fat and predisposition to develop diabetes mellitus. We have previously reported that 22 patients from 16 consanguineous pedigrees living in the northeastern region of Brazil had a homozygous 669insA mutation in the Seipin gene (BSCL2 locus), while all of the 10 investigated subjects from the southeastern region were homozygous for a 1036 bp deletion in the AGPAT2 gene (BSCL1 locus). In this study, we compared the serum insulin and insulin resistance (HOMA), leptin, triglyceride and fasting glucose levels in individuals of these two genetically distinct clusters of BSCL subjects. The onset of diabetes was also estimated. The fasting glucose and triglyceride levels were not significantly different in these groups. Significant differences were detected for leptin, insulin and insulin resistance. BSCL1 patients presented lower serum leptin levels compared to BSCL2 patients. BSCL2 subjects had earlier onset of diabetes and higher insulin levels. In agreement, BSCL2 patients were more insulin resistant, as detected by HOMA. These results indicate phenotypic heterogeneity between BSCL1 and BSCL2 Brazilian subjects.
An intestinal lipodystrophy induced by dietary fat in female Mongolian gerbils (Meriones unguiculatus) was reversed to normal by myo-inositol given in the diet or by injection within 1-4 days. An increase in plasma chylomicron and lipid concentrations was observed before the occurrence of rapid disappearance of accumulated lipids from the intestine. Dietary myo-inositol also caused an increase in triacylglycerol release from everted gut sacs. Thus, myo-inositol might act on the intestine to stimulate the production and secretion of chylomicrons, travelling via the lymphatic pathway into the bloodstream. The activity of pH 9.0 microsomal lipase (EC 3.1.1.3) of gerbil intestine was decreased due to myo-inositol deficiency. The lowered activity could be restored to high levels by feeding of injecting myo-inositol in vivo. A time-course study during intestinal recovery indicates that the increase in microsomal lipase activity correlated with the rapid lipid removal phase of the intestine, but not the initial increase in plasma chylomicron and triacylglycerol concentrations.
The cause of insulin resistance in lipodystrophic diabetes is unknown but has generally been ascribed to dysfunction at either the receptor or post receptor level. In a 14 year-old girl with total acquired lipodystrophy, subcutaneous and intravenous insulin requirements approximated 600 units daily. However, circulating total and free insulin levels were not increased, and during testing by the euglycemic clamp method, the glucose response to increasing free insulin concentrations was within the range found in eight subjects with insulin-dependent diabetes. Insulin clearance during the euglycemic clamp was 43, 98, 115, and 116 mL/kg/min at each of four insulin infusion rates compared to means of 13, 13, 12, and 11 in the control subjects with diabetes. No detectable degrading activity was present in serum, and serum inhibited insulin degradation normally. Binding of insulin to IgG, IgM, and IgE was not increased, insulin binding to monocytes and erythrocytes was not sufficiently abnormal to account for the the insulin resistance, and insulin receptor increased insulin clearance or accelerated degradation of insulin by tissues.
The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.
HISTORY AND ADMISSION FINDINGS: A 29-year-old hemophiliac with HIV infection for which he was receiving antiretroviral treatment (ART) with indinavir, zidovudine and zalcitabine reported increasing swelling of the neck. Physical examination noted a soft to doughy swelling, not sensitive to pressure, extending from the neck to between the shoulder blades. INVESTIGATIONS: Ultrasonography and magnetic resonance imaging revealed the swelling to consist of an accumulation of subcutaneous fat without capsule. Cytology demonstrated benign fatty tissue. Blood triglycerides totalled 667 mg/dl. DIAGNOSIS, TREATMENT AND COURSE: The typical location, absence of a capsule and the cytological finding confirmed the clinical diagnosis of drug-induced benign symmetrical lipomatosis (BSL, also called peripheral lipodystrophy) in ART. A connection with the hyperlipoproteinaemia is supported by the observation that the patient used to have a normal fat metabolism; the onset of BSL coincided with a massive increase in triglyceride levels. The hyperglyceridaemia and clinical signs improved on a low-fat diet. CONCLUSIONS: BSL can occur in the course of ART in HIV infection, when reverse-transcriptase inhibitors or protease inhibitors are being taken. Medication should not be changed, when antiretroviral treatment is adequate. To reduce the symptoms low-fat diet should be tried, as well as administration of HMG-CoA-reductase inhibitors or, if necessary, surgical liposuction.
Cholesterol ester storage disease is a rare, inherited metabolic disorder of lipid associated with acid cholesteryl ester hydrolase deficiency. Thus far, 15 cases have been reported in the world literature. Reported here is the autopsy study of the oldest patient with this disease. The lipid storage occurred in the forms of birefringent needle-shaped crystals limited to hepatocytes and non-birefringent autofluorescent granules accumulated within the foam cells of the hepatic portal triads, duodenum, and ovaries. The cholesterol content of the liver was 16 times normal, primarily caused by increased cholesterol ester. Only trace cholesteryl ester hydrolase activity was demonstrated in the liver. An additional unique finding in our case was the presence of mesenteric lipodystrophy. Whether these two rare disorders observed in our patient represent unrelated conditions or have an etiologic association remains unknown.
Mutations in the LMNA gene encoding A-type lamins cause several diseases, including Emery-Dreifuss muscular dystrophy and Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed differentiation of 3T3-L1 preadipocytes to adipocytes in cells overexpressing wild-type lamin A as well as lamin A with amino acid substitutions at position 482 that cause FPLD. We also examined adipogenic conversion of mouse embryonic fibroblasts lacking A-type lamins. Overexpression of both wild-type and mutant lamin A inhibited lipid accumulation, triglyceride synthesis and expression of adipogenic markers. This was associated with inhibition of expression of peroxisome-proliferator-activated receptor gamma 2 (PPARgamma2) and Glut4. In contrast, embryonic fibroblasts lacking A-type lamins accumulated more intracellular lipid and exhibited elevated de novo triglyceride synthesis compared with wild-type fibroblasts. They also had increased basal phosphorylation of AKT1, a mediator of insulin signaling. We conclude that A-type lamins act as inhibitors of adipocyte differentiation, possibly by affecting PPARgamma2 and insulin signaling.
Like Mongolian gerbils (Meriones unguiculatus), Meriones libycus develop an intestinal lipodystrophy due to myo-inositol deficiency. Fat accumulation was observed in the intestine of both species when a myo-inositol-deficient diet containing coconut oil was fed to female gerbils. It began in the duodenum and gradually extended to the entire small intestine. Starvation partially removed the accumulated fats. The efficiency of fat absorption was not affected. Most of the accumulated fats were lauric acid-rich triglyceride with the fatty acid composition reflecting the pattern of the intestinal lymph triglyceride during normal transport of absorbed coconut oil. The ratio of oleic acid to linoleic acid in various intestinal lipids was increased. A marked decrease in all plasma lipid and lipoprotein concentrations, including chylomicron, was also observed. It is assumed that the intestinal fat accumulation resulted from a defect in lymphatic transport of dietary fats.
Mesenteric lipodystrophy (ML) is a rare condition characterized by a nonspecific inflammatory process that involves the root of the mesentery in a lipoma-like lesion. Presenting features of ML include abdominal pain, weight loss, nausea, vomiting, diarrhea, and constipation. This case illustrates that ML should be included in the differential diagnosis of patients with fever of unknown origin and mesenteric calcifications.