scholarly journals SUN-LB111 Comparison of Phenotype and Metabolic Abnormalities Among Familial Partial Lipodystrophy Due to LMNA or PPARG Variants

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Chandna Vasandani ◽  
Xilong Li ◽  
Hilal Sekizkardes ◽  
Rebecca Brown ◽  
Abhimanyu Garg
Keyword(s):  
Polycystic Ovarian Syndrome ◽  
Early Recognition ◽  
Skinfold Thickness ◽  
The United States ◽  
Metabolic Abnormalities ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Fat Loss ◽  
Familial Partial Lipodystrophy ◽  
Ovarian Syndrome

Abstract Familial partial lipodystrophy (FPLD), a rare autosomal dominant disorder, is characterized by marked loss of subcutaneous (sc) fat from the extremities, and predisposition to insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis. FPLD2 and FPLD3 due to causal variants in LMNA and PPARG, respectively, are the two most common subtypes. Due to extremely rare prevalence of FPLD3 and limited reports in the literature, whether there are phenotypic differences between the two subtypes remain unclear. Therefore, we compared the anthropometric measurements and prevalence of metabolic abnormalities among 32 FPLD3 subjects (4 M, 28 F; mean ± SD age, 41 ± 17.2 y; body mass index (BMI), 26 ± 4.0 kg/m2) with 271 FPLD2 subjects (66 M, 205 F; age, 37.4 ± 17.0 y; BMI, 26 ± 5.0 kg/m2) from two referral centers in the United States. As compared to those with FPLD2, FPLD3 subjects had borderline higher prevalence of hypertriglyceridemia (66% vs 84%; P = 0.063), but significantly higher prevalence of diabetes (44% vs 72%; P = 0.004), past history of acute pancreatitis (13% vs 52%; P <0.001), and polycystic ovarian syndrome (26% vs 52%; P = 0.011). As compared to FPLD2, FPLD3 subjects had similar fasting triglyceride levels (median 208 vs 255 mg/dL; P=0.15), but lower high-density lipoprotein cholesterol levels (median 37.5 vs 30 mg/dL; P = 0.001), higher fasting glucose (median 95 vs 115 mg/dL; P = 0.05) and HbA1c (median 5.7 vs 7.0 %; P = 0.005) levels. Regional body fat was measured by dual energy X-ray absorptiometry in 19 FPLD3 and 105 FPLD2 subjects. In comparison to FPLD2, FPLD3 subjects had higher total fat (median 21.6% vs 26.1 %; P = 0.018); upper limb fat (median 20.3% vs 27.3%; P = 0.003) and lower limb fat (median 16.0% vs 20.8%; P = 0.007). Skinfold thickness measurements by calipers also revealed less severe fat loss from both the upper and lower extremities in FPLD3 subjects compared to FPLD2 subjects. As compared to FPLD2, FPLD3 subjects had significantly higher triceps skinfold thickness (median 5.5 mm vs 7.5 mm; P = 0.015); and thigh skinfold thickness (median 5.8 mm vs 11.3 mm; P = 0.001). There were no significant differences in the prevalence of fatty liver, plasma alanine aminotransferase and aspartate aminotransferase levels in the two subtypes. We conclude that compared to FPLD2 subjects, those with FPLD3 have milder lipodystrophy phenotype but paradoxically present with more severe metabolic complications, especially diabetes, dyslipidemia and polycystic ovarian syndrome. It is likely that this discrepancy could be due to early recognition of FPLD2 because of severe fat loss versus initial diagnosis of FPLD3 subjects due to severe metabolic complications leading to discovery of milder fat loss.

scholarly journals Diagnostic Value of Anthropometric Measurements for Familial Partial Lipodystrophy, Dunnigan Variety

2020 ◽  
Vol 105 (7) ◽  
pp. 2132-2141
Author(s):  
Chandna Vasandani ◽  
Xilong Li ◽  
Hilal Sekizkardes ◽  
Beverley Adams-Huet ◽  
Rebecca J Brown ◽  
...  
Keyword(s):  
Lower Limb ◽  
False Negative ◽  
Skinfold Thickness ◽  
Diagnostic Value ◽  
Small Sample ◽  
Anthropometric Measurements ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Adult Females ◽  
Familial Partial Lipodystrophy

Abstract Context Familial partial lipodystrophy, Dunnigan variety (FPLD2) is a rare autosomal dominant disorder resulting from LMNA causal variants, which is characterized by loss of subcutaneous fat from the extremities and predisposition to metabolic complications. The diagnostic value of various anthropometric measurements for FPLD2 remains unknown. Objective To determine specificity and sensitivity of anthropometric measurements for the diagnosis of FPLD2. Methods We measured skinfold thickness and regional body fat by dual energy X-ray absorptiometry (DXA) in 50 adult females and 6 males with FPLD2 at UT Southwestern and compared their data with the sex- and age-matched controls from the National Health and Nutrition Examination Survey (NHANES) 1999-2010. We further compared data from 1652 unaffected females from the Dallas Heart Study and 23 females with FPLD2 from the National Institutes of Health with the NHANES data. Results The DXA-derived lower limb fat (%) had the best specificity (0.995) and sensitivity (1.0) compared with the upper limb fat, truncal fat, the ratio of lower limb to truncal fat, and triceps skinfold thickness for adult females with FPLD2. The lower limb fat below 1st percentile of NHANES females had a false-positive rate of 0.0054 and a false negative rate of 0. The diagnostic value of anthropometric parameters could not be determined for males with FPLD2 due to small sample size. Conclusions The lower limb fat (%) is the best objective anthropometric measure for diagnosing FPLD2 in females. Women with below the 1st percentile lower limb fat should undergo genetic testing for FPLD2, especially if they have metabolic complications.

scholarly journals Variable Expressivity in Type 2 Familial Partial Lipodystrophy Related to R482 and N466 Variants in the LMNA Gene

2021 ◽  
Vol 10 (6) ◽  
pp. 1259
Author(s):  
David Araújo-Vilar ◽  
Sofía Sánchez-Iglesias ◽  
Ana I. Castro ◽  
Silvia Cobelo-Gómez ◽  
Álvaro Hermida-Ameijeiras ◽  
...  
Keyword(s):  
Body Composition ◽  
Skinfold Thickness ◽  
Pathogenic Variant ◽  
The Other ◽  
Metabolic Abnormalities ◽  
Lmna Gene ◽  
Partial Lipodystrophy ◽  
Variable Expressivity ◽  
Familial Partial Lipodystrophy

Patients with Dunnigan disease (FPLD2) with a pathogenic variant affecting exon 8 of the LMNA gene are considered to have the classic disease, whereas those with variants in other exons manifest the “atypical” disease. The aim of this study was to investigate the degree of variable expressivity when comparing patients carrying the R482 and N466 variants in exon 8. Thus, 47 subjects with FPLD2 were studied: one group of 15 patients carrying the N466 variant and the other group of 32 patients with the R482 variant. Clinical, metabolic, and body composition data were compared between both groups. The thigh skinfold thickness was significantly decreased in the R482 group in comparison with the N466 group (4.2 ± 1.8 and 5.6 ± 2.0 mm, respectively, p = 0.002), with no other differences in body composition. Patients with the N466 variant showed higher triglyceride levels (177.5 [56–1937] vs. 130.0 [55–505] mg/dL, p = 0.029) and acute pancreatitis was only present in these subjects (20%). Other classic metabolic abnormalities related with the disease were present regardless of the pathogenic variant. Thus, although FPLD2 patients with the R482 and N466 variants share most of the classic characteristics, some phenotypic and metabolic differences suggest possible heterogeneity even within exon 8 of the LMNA gene.

scholarly journals Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

2021 ◽  
Vol 12 ◽  
Author(s):  
Vaia Lambadiari ◽  
Aikaterini Kountouri ◽  
Eirini Maratou ◽  
Stavros Liatis ◽  
George D. Dimitriadis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Effective Treatment ◽  
Early Recognition ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Synthetic Analogue ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Type 3

BackgroundFamilial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.Case PresentationWe present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.ConclusionsThis case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

scholarly journals UNUSUAL PRESENTATIONS OF LMNA-ASSOCIATED LIPODYSTROPHY WITH COMPLEX PHENOTYPES AND GENERALIZED FAT LOSS: WHEN THE GENETIC DIAGNOSIS UNCOVERS NOVEL FEATURES

2020 ◽  
Vol 6 (2) ◽  
pp. e79-e85
Author(s):  
Natalia Xavier S. de Andrade ◽  
Suleyman Cem Adiyaman ◽  
Berna Demir Yuksel ◽  
Carla T. Ferrari ◽  
Abdelwahab Jalal Eldin ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Pathogenic Variant ◽  
The Body ◽  
Muscle Disease ◽  
Partial Lipodystrophy ◽  
Fat Loss ◽  
Pathogenic Variants ◽  
Complex Phenotypes ◽  
Familial Partial Lipodystrophy

Objective: Lipodystrophy represents a group of rare diseases characterized by loss of body fat. While patients with generalized lipodystrophy exhibit near-total lack of fat, partial lipodystrophy is associated with selective fat loss affecting certain parts of the body. Although classical familial partial lipodystrophy (FPLD) is a well-described entity, recent reports indicate phenotypic heterogeneity among carriers of LMNA pathogenic variants. Methods: We have encountered 2 unique cases with complex phenotypes, generalized fat loss, and very low leptin levels that made the distinction between generalized versus partial lipodystrophy quite challenging. Results: We present a 61-year-old female with generalized fat loss, harboring the heterozygous pathogenic variant p.R541P (c.1622G>C) on the LMNA gene. The discovery of the pathogenic variant led to correct clinical diagnosis of her muscle disease, identification of significant heart disease, and a recommendation for the implantation of a defibrillator. She was able to start metreleptin based on her generalized fat loss pattern and demonstration of the genetic variant. Secondly, we report a 40-year-old Turkish female with generalized fat loss associated with a novel heterozygous LMNA pathogenic variant p.K486E (c.1456A>G), who developed systemic B cell follicular lymphoma. Conclusion: Clinicians need to recognize that the presence of an LMNA variant does not universally lead to FPLD type 2, but may lead to a phenotype that is more complex and may resemble more closely generalized lipo-dystrophy. Additionally, providers should recognize the multisystem features of laminopathies and should screen for these features in affected patients, especially if the variant is not at the known hotspot for FPLD type 2.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy

Metabolism ◽  
2017 ◽  
Vol 72 ◽  
pp. 109-119 ◽  
Author(s):  
Baris Akinci ◽  
Huseyin Onay ◽  
Tevfik Demir ◽  
Şenay Savas-Erdeve ◽  
Ramazan Gen ◽  
...  
Keyword(s):  
Metabolic Abnormalities ◽  
Partial Lipodystrophy ◽  
Clinical Presentations ◽  
Familial Partial Lipodystrophy ◽  
Organ Complications

scholarly journals Effect of healthy lifestyle promotion on anthropometric variables, eating behavior and cardiometabolic risk factors in women with polycystic ovarian syndrome

2020 ◽  
Vol 4 (9) ◽  
pp. S46-S53
Author(s):  
Latifa Imen Benharrat ◽  
Azzedine Senouci ◽  
Wassila Benhabib ◽  
Khedidja Mekki
Keyword(s):  
Mediterranean Diet ◽  
Eating Behavior ◽  
Polycystic Ovarian Syndrome ◽  
Cardiometabolic Risk ◽  
Healthy Lifestyle ◽  
The Body ◽  
Metabolic Abnormalities ◽  
Healthy Lifestyle Promotion ◽  
T1 And T2 ◽  
Ovarian Syndrome

Background: In women with Polycystic Ovarian Syndrome (PCOS), metabolic abnormalities are common, including insulin resistance, obesity, and dyslipidemia, suggesting an increased risk for cardiovascular disease (CVD). Objectives: To evaluate the effect of healthy lifestyle promotion on eating behavior and metabolic biomarkers in women with PCOS. Subjects and Methods: The study was carried out in 102 women (30±7 years) with PCOS. Patients received nutritional counseling based on Mediterranean diet principles and recommendations to practice a regular physical activity, and were followed up during six weeks. Dietary survey and biomarkers analysis were assessed at baseline (T0), after three weeks (T1) and 6 weeks (T2). Results: After six weeks of intervention, there was a significant decrease in total energy intake by (-30%) at T1 and (-32%) at T2 (p˂0.001), compared to baseline. Significant decrease was recorded in carbohydrates, proteins and lipids intake at T1 and T2 (p˂0.001). An increase in monounsaturated fatty acid intake was noted at T1 and T2 (p˂0.001). The body mass index (BMI) diminished at T2 (p˂0.01), and waist circumference at T1 and T2 (p˂0.001). Glucose values decreased at T1 (p˂0.05) and T2 (p˂0.001). Total cholesterol decreased at T1 (p˂0.05) and T2 (p˂0.01). HDL-C increased at T1 (p˂0.001) and T2 (p˂0.001), when CRP values remained unchanged. A decrease in Thiobarbituric acid reactive substances concentrations was observed at T1 and T2 (p˂0.05). Superoxyde Dismutase, Catalase activities and thiols amount increased at T2 (p˂0.001). Conclusion: In the long term, healthy lifestyle promotion could be beneficial to prevent or reverse the clustering of metabolic abnormalities and prevent CVD in women with PCOS. Keywords: Polycystic ovary syndrome, Metabolic abnormalities, Healthy Lifestyle, Mediterranean diet, Cardiometabolic risk.

scholarly journals Case Report: An Atypical Form of Familial Partial Lipodystrophy Type 2 Due to Mutation in the Rod Domain of Lamin A/C

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina Cecchetti ◽  
M. Rosaria D’Apice ◽  
Elena Morini ◽  
Giuseppe Novelli ◽  
Carmine Pizzi ◽  
...  
Keyword(s):  
Genetic Diagnosis ◽  
Coiled Coil ◽  
Missense Variant ◽  
Lamin A ◽  
Metabolic Complications ◽  
Partial Lipodystrophy ◽  
Atypical Form ◽  
Amino Terminal ◽  
Familial Partial Lipodystrophy

PurposeFamilial partial lipodystrophy type 2 (FPLD2) patients generally develop a wide variety of severe metabolic complications. However, they are not usually affected by primary cardiomyopathy and conduction system disturbances, although a few cases of FPLD2 and cardiomyopathy have been reported in the literature. These were all due to amino-terminal heterozygous lamin A/C mutations, which are considered as new forms of overlapping syndromes.Methods and ResultsHere we report the identification of a female patient with FPLD2 due to a heterozygous missense variant c.604G>A in the exon 3 of the LMNA gene, leading to amino acid substitution (p.Glu202Lys) in the central alpha-helical rod domain of lamin A/C with a high propensity to form coiled-coil dimers. The patient’s cardiac evaluations that followed the genetic diagnosis revealed cardiac rhythm disturbances which were promptly treated pharmacologically.ConclusionsThis report supports the idea that there are “atypical forms” of FPLD2 with cardiomyopathy, especially when a pathogenic variant affects the lamin A/C head or alpha-helical rod domain. It also highlights how increased understanding of the genotype-phenotype correlation could help clinicians to schedule personalized monitoring of the lipodystrophic patient, in order to prevent uncommon but possible devastating manifestations, including arrhythmias and sudden death.

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