683 results match your criteria Lipodystrophy Generalized


Severe aortic stenosis during leptin replacement therapy in a patient with generalized lipodystrophy-associated progeroid syndrome due to a LMNA variant: a case report.

J Diabetes Investig 2022 May 7. Epub 2022 May 7.

Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Leptin replacement therapy (LRT) has drastically improved the prognosis of patients with lipodystrophy, but pro-inflammatory properties of leptin could become evident in the long run. Here we report a 30-year-old Japanese woman with generalized lipodystrophy-associated progeroid syndrome (GLPS) due to a heterozygous LMNA variant (c.29C>T; p. Read More

View Article and Full-Text PDF

Congenital generalized lipodystrophy in two siblings from Saudi Arabia: A case report.

Clin Case Rep 2022 Apr 20;10(4):e05720. Epub 2022 Apr 20.

Jazan Endocrinology and Diabetes Center Ministry of Health Jazan Saudi Arabia.

Congenital generalized lipodystrophy type 1 (CGL1) is a very rare autosomal recessive genetic mutation with generalized lipoatrophy and metabolic complications. We report CGL1 in two Saudi female siblings with lipoatrophy, diabetes mellitus, hypertriglyceridemia, steatohepatitis, and acanthosis due to very rare homozygous 1-acylglycerol-3-phosphate O-acyltransferase β (AGPAT2) genetic variant. Read More

View Article and Full-Text PDF

Case Report: Precision COVID-19 Immunization Strategy to Overcome Individual Fragility: A Case of Generalized Lipodystrophy Type 4.

Front Immunol 2022 6;13:869042. Epub 2022 Apr 6.

Diagnostic Immunology Research Unit, Multimodal Medicine Research Area, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

A 48-year-old patient affected with congenital generalized lipodystrophy type 4 failed to respond to two doses of the BNT162b2 vaccine, consisting of lipid nanoparticle encapsulated mRNA. As the disease is caused by biallelic variants of , a molecule indispensable for lipid endocytosis and regulation, we complemented the vaccination cycle with a single dose of the Ad26.COV2 vaccine. Read More

View Article and Full-Text PDF

Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real-life experience from a national reference network.

Diabetes Obes Metab 2022 Apr 20. Epub 2022 Apr 20.

Endocrinology Department, Assistance Publique-Hôpitaux de Paris (AP-HP), Saint-Antoine University Hospital, National Reference Centre for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France.

Aim: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromes treated with metreleptin in a national reference network, in a real-life setting.

Patients And Methods: Clinical and metabolic data from patients receiving metreleptin in France were retrospectively collected, at baseline, at 1 year and at the latest follow-up during treatment.

Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD; n = 28) and partial lipodystrophy (PLD; n = 19) received metreleptin over the last decade. Read More

View Article and Full-Text PDF

Successful treatment of severe hypertriglyceridemia with icosapent ethyl in a case of congenital generalized lipodystrophy type 4.

J Pediatr Endocrinol Metab 2022 Apr 13. Epub 2022 Apr 13.

The Hospital for Sick Children Department of Paediatrics, Toronto, ON, Canada.

Objectives: Congenital generalized lipodystrophy type 4 (CGL4) is a rare autosomal recessive condition with high rates of morbidity and mortality. It is a multisystem condition associated with ventricular tachyarrhythmia, congenital myopathy, hepatitis, and metabolic profile of severe hypertriglyceridemia and insulin resistance. Metreleptin is the first line treatment, however it is unavailable in several countries. Read More

View Article and Full-Text PDF

Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution.

J Pediatr Endocrinol Metab 2022 Apr 11. Epub 2022 Apr 11.

Department of General Pediatrics and Neonatology, Centre of Child and Adolescent Medicine, Justus-Liebig-University Gießen, Giessen, Germany.

Objectives: Congenital generalized lipodystrophies (CGLs) are a heterogeneous group of rare autosomal recessive disorders characterized by near/total absence of body fat. Pathogenic variants in polymerase-I and transcript release factor gene (PTRF), or CAVIN1, is responsible for CGL4. In addition to generalized fat loss, patients with CGL4 were reported to suffer from myopathy, malignant cardiac arrhythmias, gastrointestinal disorders, and skeletal abnormalities. Read More

View Article and Full-Text PDF

BSCL2/Seipin deficiency in hearts causes cardiac energy deficit and dysfunction via inducing excessive lipid catabolism.

Clin Transl Med 2022 04;12(4):e736

Department of Physiology, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.

Background: Heart failure (HF) is one of the leading causes of death worldwide and is associated with cardiac metabolic perturbations. Human Type 2 Berardinelli-Seip Congenital Lipodystrophy (BSCL2) disease is caused by mutations in the BSCL2 gene. Global lipodystrophic Bscl2 mice exhibit hypertrophic cardiomyopathy with reduced cardiac steatosis. Read More

View Article and Full-Text PDF

The neonatal onset diabetes mellitus of Chinese neonate with congenital generalized lipodystrophy 2: a case report.

BMC Endocr Disord 2022 Mar 29;22(1):83. Epub 2022 Mar 29.

Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China.

Background: Congenital generalized lipodystrophy (CGL) is a clinically heterogeneous disorder characterized by near total absence of adipose tissue along with metabolic complications. Diabetes mellitus developed from CGL usually present between ages 15 and 20 years, and there are few reports in neonate.

Case Presentation: In this report, we described a rare clinical presentation of CGL in a 12-day-old Chinese female neonates with hyperglycemia, hyperlipidemia, and subsequently appeared diabetes, hepatomegaly and fatty liver. Read More

View Article and Full-Text PDF

Loss of thymidine phosphorylase activity disrupts adipocyte differentiation and induces insulin-resistant lipoatrophic diabetes.

BMC Med 2022 Mar 28;20(1):95. Epub 2022 Mar 28.

Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université-Inserm UMRS_938, 27 rue Chaligny 75571, 12, Paris Cedex, France.

Background: Thymidine phosphorylase (TP), encoded by the TYMP gene, is a cytosolic enzyme essential for the nucleotide salvage pathway. TP catalyzes the phosphorylation of the deoxyribonucleosides, thymidine and 2'-deoxyuridine, to thymine and uracil. Biallelic TYMP variants are responsible for Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE), an autosomal recessive disorder characterized in most patients by gastrointestinal and neurological symptoms, ultimately leading to death. Read More

View Article and Full-Text PDF

When Adipose Tissue Lets You Down: Understanding the Functions of Genes Disrupted in Lipodystrophy.

Diabetes 2022 04;71(4):589-598

Lipodystrophy syndromes are conditions in which the adipose tissue mass of an individual is altered inappropriately. The change in adipose mass can range from a relatively modest and subtle redistribution in some individuals with partial lipodystrophy to a near-complete absence of adipose tissue in the most severe forms of generalized lipodystrophy. The common feature is a disconnection between the need of the individual for a safe, healthy lipid storage capacity and the available adipose mass to perform this critical role. Read More

View Article and Full-Text PDF

Not Enough Fat: Mouse Models of Inherited Lipodystrophy.

Front Endocrinol (Lausanne) 2022 18;13:785819. Epub 2022 Feb 18.

Nantes Université, CNRS, INSERM, l'institut du thorax, Nantes, France.

Lipodystrophies belong to the heterogenous group of syndromes in which the primary defect is a generalized or partial absence of adipose tissue, which may be congenital or acquired in origin. Lipodystrophy should be considered in patients manifesting the combination of insulin resistance (with or without overt diabetes), dyslipidemia and fatty liver. Lipodystrophies are classified according to the etiology of the disease (genetic or acquired) and to the anatomical distribution of adipose tissue (generalized or partial). Read More

View Article and Full-Text PDF

Lipodystrophies in Children.

Horm Res Paediatr 2022 Feb 21. Epub 2022 Feb 21.

Background: Lipodystrophy includes a wide group of diseases characterized by reduction, absence or altered distribution of adipose tissue. Lipodystrophies are classified into generalized or partial, according to the fat distribution, and congenital or acquired, considering the aetiology.

Summary: Impaired glucose and lipid metabolism is typically present, thus severe insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis are frequent complications. Read More

View Article and Full-Text PDF
February 2022

Looking for the skeleton in the closet-rare genetic diagnoses in patients with diabetes and skeletal manifestations.

Acta Diabetol 2022 May 8;59(5):711-719. Epub 2022 Feb 8.

Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 6423906, Tel Aviv, Israel.

Aims: The precision medicine approach of tailoring treatment to the individual characteristics of each patient has been a great success in monogenic diabetes subtypes, highlighting the importance of accurate clinical and genetic diagnoses of the type of diabetes. We sought to describe three unique cases of childhood-onset diabetes in whom skeletal manifestations led to the revelation of a rare type of diabetes. METHODS : Case-scenarios and review of the literature. Read More

View Article and Full-Text PDF

Approach to the Patient With Lipodystrophy.

J Clin Endocrinol Metab 2022 May;107(6):1714-1726

Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.

Lipodystrophy constitutes a spectrum of diseases characterized by a generalized or partial absence of adipose tissue. Underscoring the role of healthy fat in maintenance of metabolic homeostasis, fat deficiency in lipodystrophy typically leads to profound metabolic disturbances including insulin resistance, hypertriglyceridemia, and ectopic fat accumulation. While rare, recent genetic studies indicate that lipodystrophy is more prevalent than has been previously thought, suggesting considerable underdiagnosis in clinical practice. Read More

View Article and Full-Text PDF

Molecular and Cellular Bases of Lipodystrophy Syndromes.

Front Endocrinol (Lausanne) 2021 3;12:803189. Epub 2022 Jan 3.

Sorbonne University, Inserm UMR_S 938, Saint-Antoine Research Centre, Cardiometabolism and Nutrition University Hospital Institute (ICAN), Paris, France.

Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Read More

View Article and Full-Text PDF

Type 2 congenital generalized lipodystrophy with a heterozygous missense NOTCH2 mutation.

Eur J Clin Nutr 2022 Jan 18. Epub 2022 Jan 18.

Yunnan Key Laboratory of Children's Major Disease Research, Kunming, China.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease with a prevalence of less than one in ten million. To our knowledge, ~500 cases, including 95% of BSCL2, have been reported in the literatures, but no types of CGL with NOTCH2 gene mutation has been described. Read More

View Article and Full-Text PDF
January 2022

Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes.

Cell Rep 2022 01;38(2):110213

Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France. Electronic address:

Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. Here, we report mitochondrial abnormalities in seipin-deficient patient cells. A subset of seipin is enriched at ER-mitochondria contact sites (MAMs) in human and mouse cells and localizes in the vicinity of calcium regulators SERCA2, IP3R, and VDAC. Read More

View Article and Full-Text PDF
January 2022

Different sites of actions make different responses to thiazolidinediones between mouse and rat models of fatty liver.

Sci Rep 2022 01 10;12(1):449. Epub 2022 Jan 10.

Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Therapeutic approach for NAFLD is limited and there are no approved drugs. Pioglitazone (PGZ), a thiazolidinedione (TZD) that acts via peroxisome proliferator activated receptor gamma (PPARγ) is the only agent that has shown consistent benefit and efficacy in clinical trials. However, the mechanism of its therapeutic effect on NAFLD remains unclear. Read More

View Article and Full-Text PDF
January 2022

Lipid Metabolism in Cancer: The Role of Acylglycerolphosphate Acyltransferases (AGPATs).

Cancers (Basel) 2022 Jan 4;14(1). Epub 2022 Jan 4.

Laboratory of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.

Altered lipid metabolism is an emerging hallmark of aggressive tumors, as rapidly proliferating cancer cells reprogram fatty acid (FA) uptake, synthesis, storage, and usage to meet their increased energy demands. Central to these adaptive changes, is the conversion of excess FA to neutral triacylglycerides (TAG) and their storage in lipid droplets (LDs). Acylglycerolphosphate acyltransferases (AGPATs), also known as lysophosphatidic acid acyltransferases (LPAATs), are a family of five enzymes that catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA), the second step of the TAG biosynthesis pathway. Read More

View Article and Full-Text PDF
January 2022

Caveolar dysfunction and lipodystrophies.

Eur J Endocrinol 2022 01 28;186(3):C1-C4. Epub 2022 Jan 28.

Division of Nutrition and Metabolic Diseases, Department of Internal Medicine and the Center for Human Nutrition, UT Southwestern Medical Center, Dallas, Texas, USA.

View Article and Full-Text PDF
January 2022

AGPAT2 interaction with CDP-diacylglycerol synthases promotes the flux of fatty acids through the CDP-diacylglycerol pathway.

Nat Commun 2021 11 25;12(1):6877. Epub 2021 Nov 25.

School of Biotechnology and Biomolecular Sciences, the University of New South Wales, Sydney, NSW, 2052, Australia.

AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the glycerol-3-phosphate pathway for the synthesis of phospholipids and triacylglycerols. AGPAT2 is the only AGPAT isoform whose loss-of-function mutations cause a severe form of human congenital generalized lipodystrophy. Paradoxically, AGPAT2 deficiency is known to dramatically increase the level of its product, PA. Read More

View Article and Full-Text PDF
November 2021

Complications of lipodystrophy syndromes.

Presse Med 2021 Nov 30;50(3):104085. Epub 2021 Oct 30.

Division of Endocrinology and Metabolism, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey. Electronic address:

Lipodystrophy syndromes are rare complex multisystem disorders caused by generalized or partial lack of adipose tissue. Adipose tissue dysfunction in lipodystrophy is associated with leptin deficiency. Lipodystrophy leads to severe metabolic problems. Read More

View Article and Full-Text PDF
November 2021

Endogenous Leptin Concentrations Poorly Predict Metreleptin Response in Patients With Partial Lipodystrophy.

J Clin Endocrinol Metab 2022 03;107(4):e1739-e1751

Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, USA.

Context: Leptin replacement with metreleptin improves glycemia and hypertriglyceridemia in severely hypoleptinemic patients with generalized lipodystrophy (GLD), but its effects are variable in partially leptin-deficient patients with partial lipodystrophy (PLD).

Objective: Compare 3 leptin assays (Study I); identify diagnostic performance of leptin assays to detect responders to metreleptin for each assay (Study II).

Design: Study I: cross-sectional analysis of average bias between leptin assays. Read More

View Article and Full-Text PDF

RNA-seq of peripheral blood mononuclear cells of congenital generalized lipodystrophy type 2 patients.

Sci Data 2021 10 13;8(1):265. Epub 2021 Oct 13.

Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.

Illumina RNA-seq analysis was used to characterize the whole transcriptomes of peripheral blood mononuclear cells (PBMCs) from patients with congenital generalized lipodystrophy. RNA-seq information for seven patients with type 2 congenital generalized lipodystrophy (CGL2; Berardinelli-Seip congenital lipodystrophy, BSCL2) was obtained and compared with similar information for seven age- and sex-matched healthy control subjects. All seven CGL2 patients carried biallelic pathogenic mutations affecting the BSCL2 gene and had clinical symptoms of varying severity. Read More

View Article and Full-Text PDF
October 2021

Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia.

Eur J Endocrinol 2021 Nov 10;185(6):841-854. Epub 2021 Nov 10.

Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France.

Objective: CAV1 encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signaling pathways. Caveolin-1 is also located at the adipocyte lipid droplet. Heterozygous pathogenic variants of CAV1 induce rare heterogeneous disorders including pulmonary arterial hypertension and neonatal progeroid syndrome. Read More

View Article and Full-Text PDF
November 2021

Reduced Endothelial Leptin Signaling Increases Vascular Adrenergic Reactivity in a Mouse Model of Congenital Generalized Lipodystrophy.

Int J Mol Sci 2021 Sep 30;22(19). Epub 2021 Sep 30.

Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA.

The adipokine leptin, which is best-known for its role in the control of metabolic function, is also a master regulator of cardiovascular function. While leptin has been approved for the treatment of metabolic disorders in patients with congenital generalized lipodystrophy (CGL), the effects of chronic leptin deficiency and the treatment on vascular contractility remain unknown. Herein, we investigated the effects of leptin deficiency and treatment (0. Read More

View Article and Full-Text PDF
September 2021

Risk factors for diabetic foot ulcers in metreleptin naïve patients with lipodystrophy.

Clin Diabetes Endocrinol 2021 Oct 1;7(1):18. Epub 2021 Oct 1.

Division of Endocrinology and Metabolism, Dokuz Eylul University Faculty of Medicine, Inciralti, Izmir, Turkey.

Aim: Patients with lipodystrophy are at high risk for chronic complications of diabetes. Recently, we have reported 18 diabetic foot ulcer episodes in 9 subjects with lipodystrophy. This current study aims to determine risk factors associated with foot ulcer development in this rare disease population. Read More

View Article and Full-Text PDF
October 2021

Bone Mineral Density in Congenital Generalized Lipodystrophy: The Role of Bone Marrow Tissue, Adipokines, and Insulin Resistance.

Int J Environ Res Public Health 2021 09 15;18(18). Epub 2021 Sep 15.

Clinical Research Unit, Walter Cantídio University Hospital, Federal University of Ceará, Fortaleza 60416200, CE, Brazil.

Congenital Generalized Lipodystrophy (CGL) is a rare syndrome characterized by the almost total absence of subcutaneous adipose tissue due to the inability of storing lipid in adipocytes. Patients present generalized lack of subcutaneous fat and normal to low weight. They evolve with severe metabolic disorders, non-alcoholic fatty liver disease, early cardiac abnormalities, and infectious complications. Read More

View Article and Full-Text PDF
September 2021

Metreleptin treatment of non-HIV lipodystrophy syndromes.

Presse Med 2021 Nov 24;50(3):104070. Epub 2021 Sep 24.

Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, F-59000 Lille, France; University of Lille, F-59000 Lille, France; INSERM U1190, European Genomic Institute for Diabetes, F-59000 Lille, France.. Electronic address:

Lipodystrophy syndromes (LS) constitute a group of rare diseases of the adipose tissue, characterized by a complete or selective deficiency of the fat mass. These disorders are associated with important insulin resistance, cardiovascular and metabolic comorbidities that impact patient's survival and quality of life. Management is challenging and includes diet, physical activity, and specific pharmacological treatment of LS-associated comorbidities. Read More

View Article and Full-Text PDF
November 2021

Genetics of lipodystrophy syndromes.

Authors:
Isabelle Jéru

Presse Med 2021 Nov 23;50(3):104074. Epub 2021 Sep 23.

Laboratoire commun de Biologie et Génétique Moléculaires, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; Sorbonne Université-Inserm UMRS_938, Centre de Recherche Saint-Antoine (CRSA), Paris 75012, France. Electronic address:

Lipodystrophic syndromes (LS) constitute a clinically and genetically heterogeneous group of diseases characterized by a loss of adipose tissue. These syndromes are usually associated with metabolic complications, which are determinant for morbidity and mortality. The classical forms of LS include partial, generalized, and progeroid lipodystrophies. Read More

View Article and Full-Text PDF
November 2021