Congenital Generalized Lipodystrophy (Berardinelli-Seip Congenital Lipodystrophy)

Congenital disorders, usually autosomal recessive, characterized by severe generalized lack of ADIPOSE TISSUE, extreme INSULIN RESISTANCE, and HYPERTRIGLYCERIDEMIA.

Also Known As:

Berardinelli-Seip Congenital Lipodystrophy; Lipodystrophy, Congenital Generalized; Berardinelli Syndrome; Berardinelli-Seip Congenital Lipodystrophy Type 1; Berardinelli-Seip Congenital Lipodystrophy Type 2; Berardinelli-Seip Congenital Lipodystrophy, Type 1; Berardinelli-Seip Congenital Lipodystrophy, Type 2; Berardinelli-Seip Syndrome; Brunzell Syndrome; Brunzell Syndrome (with Bone Cysts); Brunzell Syndrome, AGPAT2-Related; Brunzell Syndrome, BSCL2-Related; Congenital Generalized Lipodystrophy Type 1; Congenital Generalized Lipodystrophy Type 2; Congenital Lipoatrophic Diabetes; Generalized Lipodystrophy; Lipoatrophic Diabetes, Congenital; Lipodystrophy, Berardinelli-Seip Congenital, Type 1; Lipodystrophy, Berardinelli-Seip Congenital, Type 2; Lipodystrophy, Congenital Generalized, Type 1; Lipodystrophy, Congenital Generalized, Type 2; Lipodystrophy, Total, And Acromegaloid Gigantism; Seip Syndrome; Total Lipodystrophy; Total Lipodystrophy and Acromegaloid Gigantism; AGPAT2-Related Brunzell Syndrome; BSCL2-Related Brunzell Syndrome; Berardinelli Seip Congenital Lipodystrophy; Berardinelli Seip Congenital Lipodystrophy Type 1; Berardinelli Seip Congenital Lipodystrophy Type 2; Berardinelli Seip Congenital Lipodystrophy, Type 1; Berardinelli Seip Congenital Lipodystrophy, Type 2; Berardinelli Seip Syndrome; Brunzell Syndrome, AGPAT2 Related; Brunzell Syndrome, BSCL2 Related; Congenital Generalized Lipodystrophies; Congenital Lipoatrophic Diabete; Congenital Lipodystrophy, Berardinelli-Seip; Diabete, Congenital Lipoatrophic; Diabetes, Congenital Lipoatrophic; Generalized Lipodystrophies; Generalized Lipodystrophies, Congenital; Generalized Lipodystrophy, Congenital; Lipoatrophic Diabete, Congenital; Lipodystrophies, Congenital Generalized; Lipodystrophies, Generalized; Lipodystrophies, Total; Lipodystrophy, Berardinelli-Seip Congenital; Lipodystrophy, Generalized; Lipodystrophy, Total; Syndrome, AGPAT2-Related Brunzell; Syndrome, BSCL2-Related Brunzell; Syndrome, Berardinelli; Syndrome, Berardinelli-Seip; Syndrome, Brunzell; Syndrome, Brunzell (with Bone Cysts); Syndrome, Seip; Total Lipodystrophies

Networked: 255 relevant articles (13 outcomes, 23 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Insulin Resistance
2.	Lipodystrophy
3.	Metabolic Diseases (Metabolic Disease)
4.	Diabetes Mellitus
5.	Lipoatrophic Diabetes Mellitus

Experts

1.	Garg, Abhimanyu: 23 articles (01/2022 - 05/2002)
2.	Gorden, Phillip: 18 articles (01/2018 - 10/2003)
3.	Brown, Rebecca J: 16 articles (06/2022 - 08/2014)
4.	Agarwal, Anil K: 12 articles (01/2022 - 05/2002)
5.	Cochran, Elaine: 11 articles (11/2021 - 02/2005)
6.	Oral, Elif A: 10 articles (01/2021 - 03/2010)
7.	Akinci, Baris: 8 articles (01/2021 - 01/2015)
8.	Cochran, Elaine K: 8 articles (03/2017 - 07/2004)
9.	Simha, Vinaya: 8 articles (01/2016 - 11/2002)
10.	Magré, Jocelyne: 6 articles (11/2022 - 04/2008)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Congenital Generalized Lipodystrophy:

1.	LeptinIBA 01/01/2015 - "Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. " 07/01/2005 - "Long-term efficacy of leptin replacement in patients with generalized lipodystrophy." 01/01/2015 - "Previous uncontrolled open-label studies have demonstrated that physiological doses of leptin repletion have corrected many of the metabolic derangements observed in subjects with rare fat maldistribution syndromes such as generalized lipodystrophy. " 04/01/2007 - "Our goal was to observe changes in metabolic parameters for patients with FPLD on long-term leptin replacement and to compare the metabolic characteristics seen in FPLD with those seen in generalized lipodystrophy (GL) from our previous studies. " 09/30/2021 - "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. "
2.	metreleptinIBA 01/01/2018 - "The purpose of this study is to summarize the effectiveness and safety of metreleptin in patients with congenital or acquired generalized lipodystrophy. " 01/01/2015 - "Following many successful trials, the US Food and Drug Administration approved metreleptin for the treatment of non-HIV-related forms of generalized lipodystrophy. " 01/01/2023 - "Metreleptin Treatment in a Boy with Congenital Generalized Lipodystrophy due to Homozygous c.465_468delGACT (p.T156Rfs*8) Mutation in the BSCL2 Gene: Results From the First-year" 07/26/2022 - "Congenital generalized lipodystrophy type 4 due to a novel PTRF/CAVIN1 pathogenic variant in a child: effects of metreleptin substitution." 09/01/2020 - "Metreleptin replacement treatment improves quality of life and psychological well-being in congenital generalized lipodystrophy."
3.	recombinant methionyl human leptinIBA 02/01/2005 - "Ten females and 4 males with generalized lipodystrophy were treated with recombinant methionyl human leptin (r-metHuLeptin) in physiologic doses in an open-labeled study for a period of 12 and 8 months, respectively. " 07/01/2005 - "Fifteen patients with generalized lipodystrophy were treated with twice-daily recombinant methionyl human leptin (r-metHuLeptin) for 12 months. " 08/01/2007 - "The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels. " 01/01/2019 - "Metreleptin, a recombinant methionyl -human -leptin, was approved to treat patients with generalized lipodystrophy (GL) in February 2014. " 07/01/2015 - "This review covers the physiology of leptin, the pharmacologic properties of recombinant methionyl human leptin (R-metHu-Leptin, metreleptin), evidence for metreleptin's efficacy in the treatment of generalized lipodystrophy from both completed and ongoing clinical trials, safety concerns, and future directions in metreleptin research. "
4.	LipidsIBA 01/01/2023 - "The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. " 01/01/2021 - "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. " 01/01/2018 - "Seipin, the gene that causes Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. " 01/01/2014 - "Association between Pro12Ala, Pvull, Avall, Sstl and ADIPOQ single-nucleotide polymorphisms with lipid and glycemic profiles of patients with Berardinelli-Seip syndrome." 11/01/2013 - "Berardinelli-Seip syndrome is a rare autosomal recessive disease characterized by inadequate metabolism and inefficient storing of lipids in fat cells, generating accumulation of fat in organs such as the liver, spleen, pancreas, heart, arterial endothelium and skin. "
5.	Insulin (Novolin)FDA Link 06/13/2021 - "Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. " 12/01/2016 - "Conversations between insulin and bone: Potential mechanism of high bone density in patients with Berardinelli-Seip Congenital Lipodystrophy." 06/01/1996 - "The results suggest a postreceptor defect in the action of insulin in congenital generalized lipodystrophy. " 06/01/1996 - "Acquired generalized lipodystrophy seems to be an autoimmune disorder with secondary destruction of the adipose organ: the anabolic syndrome with insulin-resistant diabetes is secondary. " 10/01/1987 - "Insulin specific receptors on red blood cells and cultured fibroblasts were investigated in a male infant affected of congenital generalized lipodystrophy (CGL). "
6.	Dietary Fats (Dietary Fat)IBA 09/01/1983 - "Previous studies have suggested that reduction of dietary fat intake, with or without caloric restriction, may lead to improvement in certain of the characteristic abnormalities that accompany total lipodystrophy (TLD). "
7.	Lamin Type A (Lamin A)IBA 04/14/2021 - "Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, atypical progeroid syndrome (APS) and generalized lipodystrophy-associated progeroid syndrome (GLPS). " 01/01/2001 - "The two lipodystrophic syndromes which molecular defect is identified are the familial partial lipodystrophy of the Dunnigan type, due to mutations of the lamin A/C gene, and the congenital generalized lipodystrophy, linked to alterations in the protein seipin. " 10/01/2003 - "Monogenic forms of insulin resistance, such as familial partial lipodystrophy, which results from mutations in either LMNA (encoding lamin A/C) or PPARG (encoding peroxisome proliferator-activated receptor gamma), and congenital generalized lipodystrophy, which results from mutations in either AGPAT2 (encoding 1-acylglycerol-3-phosphate O-acyltransferase) or BSCL2 (encoding seipin), can display features seen in the common metabolic syndrome. " 10/01/2010 - "Mandibuloacral dysplasia (MAD) is an autosomal recessive progeroid disorder associated with type A (partial) or B (generalized) lipodystrophy and is due to mutations in lamin A/C (LMNA) or zinc metalloproteinase (ZMPSTE24) genes. " 04/01/2008 - "Recombinant human leptin (r-metHuLeptin) therapy has been shown to be effective in treating metabolic abnormalities associated with congenital or acquired generalized lipodystrophy and PL associated with lamin A/C (LMNA) gene mutations or highly active antiretroviral therapy (HAART). "
8.	FenfluramineIBA 06/01/1977 - "Congenital generalized lipodystrophy and experimental lipoatrophic diabetes in rabbits treated successfully with fenfluramine." 05/01/1978 - "Fat cell size and lipid composition of subcutaneous tissue from 3 patients with congenital generalized lipodystrophy have been measured before and after treatment with either pimozide, fenfluramine or hypophysectomy. "
9.	Triglycerides (Triacylglycerol)IBA 07/01/2003 - "Congenital generalized lipodystrophy: significance of triglyceride biosynthetic pathways." 05/01/2002 - "We conclude that mutations in AGPAT2 may cause congenital generalized lipodystrophy by inhibiting triacylglycerol synthesis and storage in adipocytes." 04/01/2002 - "Triglyceride-induced diabetes mellitus in congenital generalized lipodystrophy." 10/01/2013 - "Generalized lipodystrophy is a rare disorder characterized by marked loss of adipose tissue with reduced triglyceride storage capacity, leading to a severe form of metabolic syndrome including hypertriglyceridemia, insulin resistance, type 2 diabetes mellitus, and hepatic steatosis. " 12/01/2022 - "Seipin is an endoplasmic reticulum protein that forms oligomeric complexes at endoplasmic reticulum-LD contact sites, and seipin deficiency results in severe alterations in LD maturation and morphology as seen in Berardinelli-Seip congenital lipodystrophy type 2. While seipin is critical for triacylglycerol-rich LD formation, no studies have directly addressed whether seipin is important for CE-rich LD biogenesis. "
10.	Proteins (Proteins, Gene)FDA Link 11/01/2022 - "Deficiency of the endoplasmic reticulum (ER) protein seipin results in generalized lipodystrophy by incompletely understood mechanisms. " 11/02/2020 - "SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. " 11/01/2016 - "Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) is caused by loss-of-function mutations in SEIPIN, a protein implicated in both adipogenesis and lipid droplet expansion but whose molecular function remains obscure. " 03/15/2014 - "The human congenital generalized lipodystrophy type 2 protein seipin (Fld1 in budding yeast) controls lipid droplet (LD) size through an unknown mechanism. " 01/01/2014 - "Disruption of the gene BSCL2, which encodes the protein seipin, causes severe generalized lipodystrophy in humans with a near complete absence of adipose tissue. "

Therapies and Procedures

1.	Therapeutics 01/01/2020 - "Acquired generalized lipodystrophy can occur during anti-PD1 therapy and is associated with severe metabolic complications. " 01/26/2018 - "Clinical outcome in a series of pediatric patients with congenital generalized lipodystrophies treated with dietary therapy." 08/01/2007 - "Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. " 05/01/2005 - "HIV-positive adult patients with body fat redistribution (lipodystrophy syndrome) associated with antiretroviral therapy reported their total non-lipodystrophy symptoms and side effects and completed measures assessing body fat changes (yielding Atrophy, Hypertrophy and Total Lipodystrophy scores), mental health and quality of life. " 03/01/2017 - "In a prospective open-label study, we studied the effects of metreleptin therapy (16-32 weeks) on plasma ANGPTL3/4 in patients with generalized lipodystrophy. "
2.	Caloric Restriction 09/01/1983 - "Previous studies have suggested that reduction of dietary fat intake, with or without caloric restriction, may lead to improvement in certain of the characteristic abnormalities that accompany total lipodystrophy (TLD). "
3.	Highly Active Antiretroviral Therapy (HAART) 01/01/2015 - "Pronounced complications of insulin resistance, dyslipidemia and fatty liver are observed in patients suffering from congenital or acquired generalized lipodystrophy while somewhat less pronounced abnormalities are associated with human immunodeficiency virus (HIV) and the use of highly active antiretroviral therapy, the so-called HIV-associated lipodystrophy. " 04/01/2008 - "Recombinant human leptin (r-metHuLeptin) therapy has been shown to be effective in treating metabolic abnormalities associated with congenital or acquired generalized lipodystrophy and PL associated with lamin A/C (LMNA) gene mutations or highly active antiretroviral therapy (HAART). "
4.	Catheter Ablation 11/01/2022 - "Child With Congenital Generalized Lipodystrophy Type 4 for Electrophysiology Study and Catheter Ablation: Anesthetic Challenges."
5.	Injections 01/01/2020 - "We conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. "