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

Akıncı, Barış; Önay, Hüseyin; Demir, Tevfik; Savaş‐Erdeve, Şenay; Gen, Ramazan; Şimşir, Ilgın Yıldırım; Keskin, Fatma Ela; Ertürk, Mehmet; Üzüm, Ayşe Kubat; Yaylalı, Güzin Fidan; Kutbay, Nilüfer Özdemir; Atik, Tahir; Özen, Samim; Yürekli, Banu Şarer; Apaydın, Tuğçe; Altay, Canan; Akıncı, Gülçin; Demir, Leyla; Çömlekçi, Abdurrahman; Seçil, Mustafa; Oral, Elif A.

doi:10.1016/j.metabol.2017.04.010

Cited by 63 publications

(58 citation statements)

References 39 publications

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“…In contrast, most affected individuals with FPLD type 2 have a rounded face, double chin, increased fat around the neck, and slender arms that can lead to misdiagnosis of Cushing syndrome. One exception to this is that loss of facial fat has been previously reported in carriers of the heterozygous missense LMNA pathogenic variant at p.R349W in exon 6 which probably is more progeroid in presentation than other variants (11). Despite the general-ized fat loss, an accumulation of subcutaneous fat in the mons pubis region despite loss of fat tissue in the surrounding extremity regions may be a clue about the involvement of the LMNA gene in similar patients (6).…”

Section: Discussionmentioning

confidence: 91%

Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Andrade

Adiyaman

Yuksel

et al. 2020

AACE Clinical Case Reports

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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.

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Section: Discussionmentioning

confidence: 91%

Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Andrade

Adiyaman

Yuksel

et al. 2020

AACE Clinical Case Reports

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“…Normal weight metabolically unhealthy (NWMU) people have recently been characterized by genetic, anthropometric and body composition methods [ 24 – 27 ]. These studies highlight that common genetic variants associated with indices of IR or fat distribution are associated with metabolic features [ 25 ] and lower adiposity and BMI [ 24 , 27 ], such as that found in monogenic lipodystrophies [ 1 , 20 , 28 ]. In addition, Stefan et al [ 26 ] studied a cohort of 981 subjects who were at risk for metabolic diseases using whole-body MRI.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy

Godoy-Matos

Valério

Moreira

et al. 2018

Diabetol Metab Syndr

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BackgroundTo study pancreatic fat deposition and beta-cell function in familial partial lipodystrophy (FPLD) patients.MethodsIn a cross-sectional study, eleven patients with FPLD, and eight healthy volunteers were matched for age and body mass index and studied at a referral center. Body composition was assessed using dual-energy X-ray absorptiometry and the Dixon method of magnetic resonance imaging was used to quantify pancreatic and liver fat. Fasting plasma glucose, insulin, leptin, lipids and homeostasis model assessment of insulin resistance values were measured, and an oral glucose tolerance test was performed. The insulinogenic index, Matsuda insulin sensitivity index and beta-cell disposition index were calculated.ResultsThe FPLD group presented a higher waist-to-hip ratio and fat mass ratio and lower total, truncal and lower-limb fat masses. Pancreatic and liver fat contents (log transformed) were significantly higher in the FPLD group (5.26 ± 1.5 vs. 4.08 ± 0.64, p = 0.034 and 0.77 ± 0.50 vs. 0.41 ± 0.18, p = 0.056, respectively). Pancreatic fat was inversely related to the DI (r = − 0.53, p = 0.027) and HDL-cholesterol (r = − 0.63, p = 0.003) and directly related to WHR (r = 0.60; p = 0.009), HbA1c (r = 0.58; p = 0.01) and serum triglyceride (r = 0.48, p = 0.034). Higher triglyceride and lower HDL-cholesterol levels were observed in the FPLD group.ConclusionsThis study demonstrated for the first time that pancreatic fat deposition is increased in FPLD. Moreover, an inverse relationship was demonstrated between pancreatic fat and beta-cell function. The findings of this study may be consistent with the expandability hypothesis and the twin cycle hypothesis.

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“…Loss of adipose tissue is predominantly observed in the upper and lower extremities. Patients may exhibit accumulation of fat in certain areas such as the face and neck, and perineal and intra-abdominal depots (2,4,30,31,32). A Cushingoid-appearance can be observed, due to thin limbs, facial fat accumulation and increased fat in the dorsocervical region resembling a 'buffalo hump' (5).…”

Section: Familial Partial Lipodystrophymentioning

confidence: 99%

“…A Cushingoid-appearance can be observed, due to thin limbs, facial fat accumulation and increased fat in the dorsocervical region resembling a 'buffalo hump' (5). The partial loss of fat may be apparent in early life, but typically becomes more pronounced over time in FPLD, and most patients start to lose adipose tissue after puberty (30). For this reason, it is difficult to recognize these patients in childhood.…”

Section: Familial Partial Lipodystrophymentioning

confidence: 99%

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Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People

Özen

Akıncı

Oral

2020

Jcrpe

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Lipodystrophy is a heterogeneous group of disorders characterized by lack of body fat in characteristic patterns, which can be genetic or acquired. Lipodystrophy is associated with insulin resistance that can develop in childhood and adolescence, and usually leads to severe metabolic complications. Diabetes mellitus, hypertriglyceridemia, and hepatic steatosis ordinarily develop in these patients, and most girls suffer from menstrual abnormalities. Severe complications develop at a relatively young age, which include episodes of acute pancreatitis, renal failure, cirrhosis, and complex cardiovascular diseases, and all of these are associated with serious morbidity. Treatment of lipodystrophy consists of medical nutritional therapy, exercise, and the use of anti-hyperglycemic and lipid-lowering agents. New treatment modalities, such as metreleptin replacement, promise much in the treatment of metabolic abnormalities secondary to lipodystrophy. Current challenges in the management of lipodystrophy in children and adolescents include, but are not limited to: (1) establishing specialized centers with experience in providing care for lipodystrophy presenting in childhood and adolescence; (2) optimizing algorithms that can provide some guidance for the use of standard and novel therapies to ensure adequate metabolic control and to prevent complications; (3) educating patients and their parents about lipodystrophy management; (4) improving patient adherence to chronic therapies; (5) reducing barriers to access to novel treatments; and (5) improving the quality of life of these patients and their families.

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

Cited by 63 publications

References 39 publications

Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Unusual Presentations of LMNA-Associated Lipodystrophy with Complex Phenotypes and Generalized Fat Loss: When the Genetic Diagnosis Uncovers Novel Features

Pancreatic fat deposition is increased and related to beta-cell function in women with familial partial lipodystrophy

Current Diagnosis, Treatment and Clinical Challenges in the Management of Lipodystrophy Syndromes in Children and Young People

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