Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review

Fernández-Pombo, Antía; Díaz-López, Everardo Josué; Castro, Ana; Sánchez-Iglesias, Sofía; Cobelo-Gómez, Silvia; Prado-Moraña, Teresa; Araújo‐Vilar, David

doi:10.3390/cells12050725

Cited by 16 publications

(10 citation statements)

References 153 publications

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“…Hyperlipidemia or dyslipidemia has also been reported in carriers of LMNA mutations [ 12 , 13 ]. Hyperlipidemia can secondarily cause steatosis.…”

Section: Discussionmentioning

confidence: 99%

Novel Phenotype of LMNA Variant c.154C>G Affecting Heart, Liver, and Lipid and Iron Metabolism: A Case Report

Finsterer¹,

Pölzl²

2023

Cureus

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Mutations in the LMNA gene cause heterogeneous phenotypes such as myopathy, progeroid syndromes, hereditary neuropathies, cardiomyopathies, or lipodystrophies. A specific LMNA mutation manifesting as dilated cardiomyopathy (dCMP), and iron metabolism disorder has not been reported. The patient is a 50-year-old female with palpitations and fatigue since childhood, hyperlipidemia for 25 years, gastroesophageal reflux for 20 years, arterial hypertension for eight years, and iron deficiency for one year, requiring intravenous iron supplementation. Family history was positive for dCMP, malignant ventricular arrhythmias (MVAs), and sudden cardiac death (SCD). She was diagnosed with dCMP at the age of 49. Genetic workup revealed the variant c.154C>G (p.Leu52Val) in LMNA , which was also found in two female cousins. Because of ventricular tachycardia in the long-term ECG recordings, an implantable cardioverter-defibrillator (ICD) was implanted in addition to antiarrhythmic, antihypertensive, heart failure, and lipid-lowering treatment. With this therapy, the patient remained in stable condition during the one-year follow-up and was able to successfully carry out her job. In summary, this case shows that the variant c.154C>G (p.Leu52Val) in LMNA manifests not only with dCMP, but also with hyperlipidemia, steatosis, gastroesophageal reflux, arterial hypertension, and iron deficiency. Primary prophylaxis with an ICD and additional symptomatic treatment can stabilise the condition and eventually prevent familial SCD.

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“…Hyperlipidemia or dyslipidemia has also been reported in carriers of LMNA mutations [ 12 , 13 ]. Hyperlipidemia can secondarily cause steatosis.…”

Section: Discussionmentioning

confidence: 99%

Novel Phenotype of LMNA Variant c.154C>G Affecting Heart, Liver, and Lipid and Iron Metabolism: A Case Report

Finsterer¹,

Pölzl²

2023

Cureus

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“…Metabolic stress caused by mutations in LMNA is usually associated with altered lipid metabolism in certain types of laminopathies, such as familial partial lipodystrophy type 2 (FPLD2). The muscle cells and adipocytes in FLPD2 exhibit features of a diabetes‐related metabolic disorder, including loss of body fat, glucose intolerance, high blood pressure, high plasma triglyceride, low HDL cholesterol levels, and loss of insulin sensitivity 233 . The causes of this lipotoxic metabolic stress in FPLD2 are attributed to several cellular pathways, namely impaired adipocyte differentiation (represented by lower expression of PPAR‐γ2, GLUT4, and higher phosphorylation of AKT1), 234 lower production of leptins 233 and retinol‐binding proteins (RBPs), 235 higher expression of irisin, 236 and deregulated transport of free fatty acids to different cells 237 …”

Section: The Role Of Stress Factors In Laminopathiesmentioning

confidence: 99%

Nuclear proteostasis imbalance in laminopathy‐associated premature aging diseases

Pande

Ghosh

2023

The FASEB Journal

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Laminopathies are a group of rare genetic disorders with heterogeneous clinical phenotypes such as premature aging, cardiomyopathy, lipodystrophy, muscular dystrophy, microcephaly, epilepsy, and so on. The cellular phenomena associated with laminopathy invariably show disruption of nucleoskeleton of lamina due to deregulated expression, localization, function, and interaction of mutant lamin proteins. Impaired spatial and temporal tethering of lamin proteins to the lamina or nucleoplasmic aggregation of lamins are the primary molecular events that can trigger nuclear proteotoxicity by modulating differential protein–protein interactions, sequestering quality control proteins, and initiating a cascade of abnormal post‐translational modifications. Clearly, laminopathic cells exhibit moderate to high nuclear proteotoxicity, raising the question of whether an imbalance in nuclear proteostasis is involved in laminopathic diseases, particularly in diseases of early aging such as HGPS and laminopathy‐associated premature aging. Here, we review nuclear proteostasis and its deregulation in the context of lamin proteins and laminopathies.

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“…Patients with FPLD2 show progressive fat redistribution beginning around puberty, as they lose fat from the trunk, limbs, and buttocks while gaining fat in the face, neck, axillae, and visceral organs [5]. Diagnosis of the clinical phenotype with accompanying hormonal and metabolic derangements is critical for reducing the increased risk of organ involvement, which may lead to serious complications, including cardiovascular disease, cirrhosis, and pancreatitis, among others [5, 6]. Female patients are more severely affected than males [7].…”

Section: Introductionmentioning

confidence: 99%

“…There is currently no treatment available for partial lipodystrophy syndromes in the USA; general measures are based on exercise and a balanced [2] diet. While metreleptin is the only drug approved specifically for generalized lipodystrophy in the USA [1, 5], its use in certain conditions, such as preconception or pregnancy, is still controversial [5, 10].…”

Section: Introductionmentioning

confidence: 99%

“…Although diet is the primary intervention, there are no guidelines and insufficient evidence to recommend any specific dietary approach [1, 5, 11]. Very-low-calorie diet (VLCD) (≤800 kcal/day) has been shown to have beneficial pleiotropic effects, including on glucose and lipid metabolism in individuals with obesity, even with reports of remission in patients with type 2 diabetes [12, 13].…”

Section: Introductionmentioning

confidence: 99%

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A Very-Low-Calorie Diet Can Cause Remission of Diabetes Mellitus and Hypertriglyceridemia in Familial Partial Lipodystrophy

Foss-Freitas,

Besci,

Meral

et al. 2023

Obes Facts

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There is no strong evidence that any specific diet is the preferred treatment for lipodystrophy syndromes. Here we remark on the benefits of a very-low calorie diet (VLCD) in a patient with familial partial lipodystrophy type 2 (FPLD2). A 38-year-old female diagnosed with FPLD2, with a history of multiple comorbidities, underwent 16 weeks of VLCD with a short-term goal of improving her metabolic state rapidly to achieve pregnancy by in-vitro fertilization (IVF). We observed a reduction of 12.3kg in body weight and 1.4% in HbA1c. The decrease in the area under the curves of insulin (-33.2%), triglycerides (-40.7%), and free fatty acids (-34%) were very remarkable. Total body fat was reduced by 16%, and liver fat by 80%. Her egg retrieval rate and quality during IVF were far superior to past hyperstimulation. Our data encourage the use of this medical approach for other patients with similar metabolic and reproductive abnormalities due to adipose tissue insufficiency.

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Clinical Spectrum of LMNA-Associated Type 2 Familial Partial Lipodystrophy: A Systematic Review

Cited by 16 publications

References 153 publications

Novel Phenotype of LMNA Variant c.154C>G Affecting Heart, Liver, and Lipid and Iron Metabolism: A Case Report

Novel Phenotype of LMNA Variant c.154C>G Affecting Heart, Liver, and Lipid and Iron Metabolism: A Case Report

Nuclear proteostasis imbalance in laminopathy‐associated premature aging diseases

A Very-Low-Calorie Diet Can Cause Remission of Diabetes Mellitus and Hypertriglyceridemia in Familial Partial Lipodystrophy

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