scholarly journals SAT-622 Heterogeneity of Familial Partial Lipodystrophy Type 2 from a Genotype-Phenotype Perspective

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Maria Cristina Foss de Freitas ◽  
Abdelwahab Jalal Eldin ◽  
Baris Akinci ◽  
Callie Corsa ◽  
Ormond A MacDougald ◽  
...  
Keyword(s):  
Body Composition ◽  
Hepatic Steatosis ◽  
Clinical Manifestation ◽  
Fat Free Mass ◽  
Partial Lipodystrophy ◽  
Pathogenic Variants ◽  
Number Of Patients ◽  
Familial Partial Lipodystrophy ◽  
Total Fat

Abstract Phenotypic heterogeneity is a well-known feature of Familial Partial Lipodystrophy Type 2 (FPLD2) which is caused by pathogenic variants in the LMNA gene. Clinical diagnosis can be challenging in some cases. Likewise, trained physicians can report differences in body composition and clinical manifestation of FPLD2, highlighting the importance of accurate phenotyping. In this study, we aimed to identify phenotype-genotype correlations in a cohort of systematically evaluated patients with FPLD2. We retrospectively evaluated 43 patients diagnosed with FPLD2 (age 50.3±16.1 years, 79.1% women). Per pathogenic variants, patients were divided into two groups; 24 with R482Q (RQ: 55 ± 3.2 years, 70.8% women) and 19 with non-R482Q (Non-RQ: 46 ± 3.2 years, 84.2% women). Non-RQ group consisted of several pathogenic LMNA variants in exons 1, and 5 through 11. Also, DEXA parameters were studied in a subgroup of 19 patients with available assessments (in 11 RQ and 8 non-RQ patients) that were matched for age, sex and BMI. Patients in the RQ group were older when they were first diagnosed with lipodystrophy (48.6 ± 3.2 years and 37.4 ± 3.1 years, p = 0.03). Although the prevalence of diabetes, hepatic steatosis and other co-morbidities associated with metabolic control were similar in both groups at the time of the study, patients with RQ pathogenic variants were diagnosed later in life with diabetes (46.0 ± 4.2 years vs. 35 ± 3.5 years, p = 0.03) and hepatic steatosis (45.3 ± 6.9 years vs. 30.1 ± 3.7 years, p < 0.01. Although more pancreatitis episodes were reported in the RQ group (13 ± 3 vs. 2 ± 1, p = 0.02), the number of patients with a history of pancreatitis was similar across the groups suggesting the occurrence of recurrent pancreatitis episodes in selected patients with RQ pathogenic variant. Pain was a common complaint among the patients, but it was less severe in the RQ group (4.2±2.1 vs 2.3±2.0, p=0.05). In terms of body composition, patients with RQ pathogenic variants had greater bone mass (legs: 879 ± 59.3 g vs. 703.5 ± 33.7 g, p= 0.01; trunk 914.2 ± 65.5 g vs. 674.1 ± 28.0 g, p = 0.005, total body: 2643.7 ± 158.9 g vs. 2140.6 ± 78.4 g, p = 0.005) and higher fat mass in the legs (19 vs. 14%, p = 0.02). Similarly, patients with RQ pathogenic variants had less lean percentage (76 vs. 81%, p = 0.009), and accordingly, less fat-free mass percentage (80 vs. 85%, p = 0.02) in the legs. Total fat-free mass of the RQ group was also lower (66 vs. 76%, p = 0.0009). Genotype-phenotype characterization is important not only for understanding the natural history and clinical manifestation of the disease but also for establishing more accurate and precise diagnostic criteria or therapeutic approaches. Our data suggest more fat preservation in LMNA R482Q carriers, presumably leading to a later diagnosis of lipodystrophy and metabolic abnormalities. More studies are needed to confirm the differences observed in body composition.

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.

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.

Level of physical activity, body composition and abdominal resistance of women with familial partial lipodystrophy of the Dunnigan type

2010 ◽  
Vol 44 (14) ◽  
pp. i4-i4
Author(s):  
L. Z. Monteiro ◽  
F. A. Pereira ◽  
M. C. Freitas-Foss ◽  
R. M. Montengro ◽  
A. I. A. Medeiros ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Composition ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy

scholarly journals Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1947
Author(s):  
Alice-Anaïs Varlet ◽  
Emmanuèle Helfer ◽  
Catherine Badens
Keyword(s):  
Mechanical Properties ◽  
Signaling Pathways ◽  
Metabolic Disorders ◽  
Lamin A ◽  
Partial Lipodystrophy ◽  
Familial Partial Lipodystrophy ◽  
Atherosclerotic Cardiovascular Diseases ◽  
Almost All ◽  
Type V

Laminopathies are rare and heterogeneous diseases affecting one to almost all tissues, as in Progeria, and sharing certain features such as metabolic disorders and a predisposition to atherosclerotic cardiovascular diseases. These two features are the main characteristics of the adipose tissue-specific laminopathy called familial partial lipodystrophy type 2 (FPLD2). The only gene that is involved in FPLD2 physiopathology is the LMNA gene, with at least 20 mutations that are considered pathogenic. LMNA encodes the type V intermediate filament lamin A/C, which is incorporated into the lamina meshwork lining the inner membrane of the nuclear envelope. Lamin A/C is involved in the regulation of cellular mechanical properties through the control of nuclear rigidity and deformability, gene modulation and chromatin organization. While recent studies have described new potential signaling pathways dependent on lamin A/C and associated with FPLD2 physiopathology, the whole picture of how the syndrome develops remains unknown. In this review, we summarize the signaling pathways involving lamin A/C that are associated with the progression of FPLD2. We also explore the links between alterations of the cellular mechanical properties and FPLD2 physiopathology. Finally, we introduce potential tools based on the exploration of cellular mechanical properties that could be redirected for FPLD2 diagnosis.

scholarly journals A specific bioelectrical impedance equation to predict body composition in Turner's syndrome

2010 ◽  
Vol 54 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Alexis D. Guedes ◽  
Bianca Bianco ◽  
Mônica V. N. Lipay ◽  
Emmanuela Q. Callou ◽  
Marise L. Castro ◽  
...  
Keyword(s):  
Body Composition ◽  
Linear Regression Analysis ◽  
Bioelectrical Impedance ◽  
Impedance Analysis ◽  
Fat Free Mass ◽  
X Ray ◽  
Great Consistency ◽  
Total Fat ◽  
Specific Equation ◽  
Standard Error Estimate

INTRODUCTION: Cardiovascular disease is one of the main causes for Turner syndrome (TS) mortality and the evaluation of its risk factors such as excess body fat and its distribution is considered one of the major aspects of the adult patient care. OBJECTIVE: To develop and validate a specific bioelectrical impedance analysis (BIA) equation to predict body composition in TS patients. SUBJECTS AND METHODS: Clinical and anthropometric data, dual-energy X-ray absorptiometry (DXA) for total fat-free mass (FFM) and BIA for resistance and reactance were obtained from 50 adult TS patients. Linear regression analysis was performed with multiple clinical and BIA data to obtain a predicting equation. RESULTS: The equation developed to estimate FFM in adult TS patients showed great consistency with DXA, elevated correlation (r = 0. 974) and determination (r² = 0. 948) coefficients and an adequate standard error estimate (SEE = 1.52 kg). CONCLUSIONS: The specific equation developed here allowed making an adequate FFM estimate in adult TS patients.

scholarly journals The Effect of a Low GI Diet on Truncal Fat Mass and Glycated Hemoglobin in South Indians with Type 2 Diabetes—A Single Centre Randomized Prospective Study

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 179 ◽  
Author(s):  
Nivedita Pavithran ◽  
Harish Kumar ◽  
Arun Somasekharan Menon ◽  
Gopala Krishna Pillai ◽  
Karimassery Ramaiyer Sundaram ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Composition ◽  
Fat Mass ◽  
South India ◽  
Glycated Hemoglobin ◽  
Diet Group ◽  
Control Group ◽  
South Indian ◽  
Total Fat

Background: There has been no previous study that has investigated the effect of a low glycemic index (LGI) diet with local recipes of South Indian cuisine on the body fat composition using dual-energy X-ray absorptiometry (DXA). Truncal obesity has been associated with the risk of metabolic disorders and cardiovascular diseases. Aim: The aim of this study was to examine the effect of a low GI diet on glycemic control and body composition in people with type 2 diabetes in South India. Method: This was a prospective and randomized controlled study that was conducted over a period of 24 weeks. A total of 40 participants were recruited from the Department of Endocrinology and Diabetes Outpatient in Kerala, South India. All the patients had type 2 diabetes and were randomly assigned and given advice and instructions to follow either a low GI diet plan (n = 18) or their usual diet, which served as control (n = 18). The advice was reinforced throughout the study period. Dietary compliance was evaluated based on a 24 h dietary recall at weeks 3, 11, 12, 18, 23, and 24. The age of the subjects ranged from 35 to 65 years. Anthropometric, body composition, and cardio-metabolic parameters were measured according to standard procedures. T-tests were conducted to compare differences between intervention and control groups and the Pearson correlation coefficient was used to evaluate associations between the variables. Results: There were significant reductions (p < 0.05) in the low GI diet compared to the control group with respect to weight, body mass index (BMI), and triceps skinfold thickness. Similarly, significant reductions were observed in the low GI diet group with respect to region, total fat, android, and gynoid fat mass and the differences between the groups were significant at p < 0.05. There was also a positive correlation between BMI and android fat mass (r = 0.745), total fat mass (r = 0.661), total truncal mass (r = 0.821), and truncal fat (r = 0.707). There was a significant reduction in glycated hemoglobin in the low GI diet group compared to the control group at p < 0.05. Conclusion: This study has demonstrated that there was a significant reduction (p < 0.05) of truncal obesity and glycated hemoglobin in patients with type 2 diabetes on a local diet of South Indian cuisine with low GI compared with the control.

Effects of an outdoor bicycle-based intervention in healthy rural Indian men with normal and low birth weight

2014 ◽  
Vol 6 (1) ◽  
pp. 27-37 ◽  
Author(s):  
C. Madsen ◽  
P. Mogensen ◽  
N. Thomas ◽  
D. L. Christensen ◽  
I. C. Bygbjerg ◽  
...  
Keyword(s):  
Body Composition ◽  
Insulin Secretion ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Exercise Training ◽  
Exercise Intervention ◽  
Young Men ◽  
Fat Free Mass ◽  
Rural India ◽  
Total Fat

Physical inactivity and low birth weight (LBW) may lead to an increased risk for developing type 2 diabetes. The extent to which LBW individuals may benefit from physical exercise training when compared with those with normal birth weight (NBW) controls is uncertain. We assessed the impact of an outdoor exercise intervention on body composition, insulin secretion and action in young men born with LBW and NBW in rural India. A total of 61 LBW and 56 NBW healthy young men were recruited into the study. The individuals were instructed to perform outdoor bicycle exercise training for 45 min every day. Fasting blood samples, intravenous glucose tolerance tests and bioimpedance body composition assessment were carried out. Physical activity was measured using combined accelerometry and heart rate monitoring during the first and the last week of the intervention. Following the exercise intervention, the LBW group displayed an increase in physical fitness [55.0 ml (O2)/kg min (52.0−58.0)−57.5 ml (O2)/kg min (54.4−60.5)] level and total fat-free mass [10.9% (8.0−13.4)−11.4% (8.0−14.6)], as well as a corresponding decline in the ratio of total fat mass/fat-free mass. In contrast, an increase in total fat percentage as well as total fat mass was observed in the NBW group. After intervention, fasting plasma insulin levels, homoeostasis model assessments (HOMA) of insulin resistance (HOMA-IR) and insulin secretion (HOMA-IS), improved to the same extent in both the groups. In summary, young men born with LBW in rural India benefit metabolically from exercise training to an extent comparable with NBW controls.

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