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 Familial Partial Lipodystrophy: A Case Study and Review of Recent Literature

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A308-A309
Author(s):  
Ali Tipu ◽  
Farhad Hasan ◽  
Michael Grimes
Keyword(s):  
Adipose Tissue ◽  
Autosomal Dominant ◽  
Recent Literature ◽  
Subcutaneous Fat ◽  
Metabolic Abnormalities ◽  
Partial Lipodystrophy ◽  
Type 2 Dm ◽  
Familial Partial Lipodystrophy ◽  
Subcutaneous Adipose

Abstract Introduction: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by loss of subcutaneous adipose tissue, mainly from the extremities and gluteal region. FPLD is associated with a variety of metabolic abnormalities including severe hypertriglyceridemia (HTG), insulin resistance (IR), and hepatic steatosis. We present a case of FPLD and summarize recent literature on the metabolic features and their management in patients with this rare disease. Case: A 44 year old female with medical history of Type 2 DM, hypertension, hypothyroidism and recurrent pancreatitis from severe HTG was referred to our clinic. She was diagnosed with Type 2 DM in her 30s. Over the ensuing years she had significant IR requiring increasing doses of concentrated insulin (up to 250 units/day). She reported progressive loss of subcutaneous fat from extremities in the preceding 2–3 years. She had recurrent pancreatitis, including a recent hospitalization with TG>8000 mg/dL. On examination, she had typical features of FPLD including loss of subcutaneous adipose tissue from upper and lower extremities including gluteal region, visible skeletal muscles and veins in the extremities, and neck and truncal obesity (Fig. 1). Family history was significant for similar physical and metabolic manifestations in her father and brother. For HTG, she is treated with fibrates and high intensity statin. We avoided the use of fish oil in the patient, because she did not feel well when she was previously on this. Results of the genetic testing are pending. Discussion: FPLD is rare, predominantly autosomal dominant, disorder characterized phenotypically by variable loss of subcutaneous fat and metabolically by severe HTG and insulin resistance. The severity of metabolic derangements is proportional to the degree of the lipodystrophy. The proposed mechanism is limited capacity of adipose tissue to store fat leading to ectopic fat deposition, lipotoxicity and vascular inflammation. Diagnosis is often clinical, especially the loss of subcutaneous fat in the extremities and signs of IR, and is confirmed by genetic testing. Dunnigan syndrome is the most common type of FPLD, which occurs from an autosomal dominant missense mutation in lamin A/C (LMNA). Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much less common. Treatment of FPLD is challenging, and mostly focuses on managing the metabolic abnormalities. Recent evidence suggests that fish oil may in fact worsen HTG when the main defect driving increased TG is impaired chylomicron clearance, which our patient had on lipid NMR profile. Metreleptin, a human leptin analog, has recently been approved for the management of FPLD with evidence of improved metabolic abnormalities. Recent data also suggests that GLP1 agonists and SGLT2 inhibitors improved glycemic control and reduced daily insulin requirements.

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 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.

A genome-wide linkage scan for familial partial lipodystrophy susceptibility genes in a German kindreds

2007 ◽  
Vol 30 (4) ◽  
pp. 86
Author(s):  
M. Lanktree ◽  
J. Robinson ◽  
J. Creider ◽  
H. Cao ◽  
D. Carter ◽  
...  
Keyword(s):  
Subcutaneous Fat ◽  
Visceral Obesity ◽  
Fat Distribution ◽  
Dominant Negative ◽  
Molecular Forms ◽  
Partial Lipodystrophy ◽  
Genome Wide ◽  
A Genome ◽  
Familial Partial Lipodystrophy ◽  
Promoter Mutations

Background: In Dunnigan-type familial partial lipodystrophy (FPLD) patients are born with normal fat distribution, but subcutaneous fat from extremities and gluteal regions are lost during puberty. The abnormal fat distribution leads to the development of metabolic syndrome (MetS), a cluster of phenotypes including hyperglycemia, dyslipidemia, hypertension, and visceral obesity. The study of FPLD as a monogenic model of MetS may uncover genetic risk factors of the common MetS which affects ~30% of adult North Americans. Two molecular forms of FPLD have been identified including FPLD2, resulting from heterozygous mutations in the LMNA gene, and FPLD3, resulting from both heterozygous dominant negative and haploinsufficiency mutations in the PPARG gene. However, many patients with clinically diagnosed FPLD have no mutation in either LMNA or PPARG, suggesting the involvement of additional genes in FPLD etiology. Methods: Here, we report the results of an Affymetrix 10K GeneChip microarray genome-wide linkage analysis study of a German kindred displaying the FPLD phenotype and no known lipodystrophy-causing mutations. Results: The investigation identified three chromosomal loci, namely 1q, 3p, and 9q, with non-parametric logarithm of odds (NPL) scores >2.7. While not meeting the criteria for genome-wide significance, it is interesting to note that the 1q and 3p peaks contain the LMNA and PPARG genes respectively. Conclusions: Three possible conclusions can be drawn from these results: 1) the peaks identified are spurious findings, 2) additional genes physically close to LMNA, PPARG, or within 9q, are involved in FPLD etiology, or 3) alternative disease causing mechanisms not identified by standard exon sequencing approaches, such as promoter mutations, alternative splicing, or epigenetics, are also responsible for FPLD.

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
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