320 results match your criteria Lipodystrophy Progressive

Possible added value of thyroglobulin antibody (TgAb) testing in the evaluation of thyroidal status of subjects with overweight or obesity.

J Endocrinol Invest 2022 Jul 4. Epub 2022 Jul 4.

Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.

Purpose: An increase in serum TSH concentrations in the absence of thyroid disease, named isolated hyperthyrotropinemia, is frequently observed in subjects with obesity. It is directly associated with body mass index, and it is reversible following weight loss. Autoimmune hypothyroidism is frequently associated with obesity, it is usually progressive and needs replacement treatment with L-thyroxine. Read More

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Partial lipodystrophy, severe dyslipidaemia and insulin resistant diabetes as early signs of Werner syndrome.

J Clin Lipidol 2022 Jun 19. Epub 2022 Jun 19.

Division of Genetic Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland (Drs Atallah, Good, Superti-Furga, and Tran). Electronic address:

Werner syndrome is a premature ageing disorder caused by biallelic variants in the WRN gene. WRN encodes a dual DNA helicase/exonuclease enzyme. Molecular diagnosis is commonly only made at a late disease stage in the third or fourth decade, when cardinal features have become apparent. Read More

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Role of Seipin in Human Diseases and Experimental Animal Models.

Biomolecules 2022 06 17;12(6). Epub 2022 Jun 17.

Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of Biotherapy, Sichuan University, Chengdu 610041, China.

Seipin, a protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 () gene, is famous for its key role in the biogenesis of lipid droplets and type 2 congenital generalised lipodystrophy (CGL2). gene mutations result in genetic diseases including CGL2, progressive encephalopathy with or without lipodystrophy (also called Celia's encephalopathy), and -associated motor neuron diseases. Abnormal expression of seipin has also been found in hepatic steatosis, neurodegenerative diseases, glioblastoma stroke, cardiac hypertrophy, and other diseases. Read More

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Rapid Weight Loss and Severe Failure to Thrive Mimicking Lipodystrophy Syndrome in a 1-Year-Old Taiwanese Girl with Costello Syndrome.

Children (Basel) 2022 Jun 16;9(6). Epub 2022 Jun 16.

Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan.

Costello syndrome (CS) is a type of RASopathy caused mainly by de-novo heterozygous pathogenic variants in the gene located on chromosome 11p15.5. The phenotype of CS is characterized by prenatal overgrowth, postnatal failure to thrive, curly or sparse fine hair, coarse facial features, and multisystem involvement, including cardiovascular, endocrine, and gastroenterological disorders. Read More

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Alternative splicing of BUD13 determines the severity of a developmental disorder with lipodystrophy and progeroid features.

Genet Med 2022 Jun 6. Epub 2022 Jun 6.

Centre de Génétique Humaine, Université de Franche-Comté, Besançon, France; Center of Clinical investigation 1431, National Institute of Health and Medical Research (INSERM), CHU, Besancon, France.

Purpose: In this study we aimed to identify the molecular genetic cause of a progressive multisystem disease with prominent lipodystrophy.

Methods: In total, 5 affected individuals were investigated using exome sequencing. Dermal fibroblasts were characterized using RNA sequencing, proteomics, immunoblotting, immunostaining, and electron microscopy. Read More

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Adipocyte-specific CDK7 ablation leads to progressive loss of adipose tissue and metabolic dysfunction.

FEBS Lett 2022 Jun 30;596(11):1434-1444. Epub 2022 Mar 30.

Center for Integrative Genomics, University of Lausanne, Switzerland.

Adipose tissue regulates whole-body energy homeostasis. Both lipodystrophy and obesity, the extreme and opposite aspects of adipose tissue dysfunction, result in metabolic disorders: insulin resistance and hepatic steatosis. Cyclin-dependent kinases (CDKs) have been reported to be involved in adipose tissue development and functions. Read More

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Genetic and cytometric analyses of subcutaneous adipose tissue in patients with hemophilia and HIV-associated lipodystrophy.

AIDS Res Ther 2022 03 4;19(1):14. Epub 2022 Mar 4.

Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke-Shi, Tochigi, 329-0498, Japan.

Background: The authors recently performed plastic surgeries for a small number of patients with hemophilia, HIV infection, and morphologic evidence of lipodystrophy. Because the pathophysiological mechanism of HIV-associated lipodystrophy remains to be elucidated, we analyzed subcutaneous adipose tissues from the patients.

Methods: All six patients had previously been treated with older nucleoside analogue reverse-transcriptase inhibitors (NRTIs; stavudine, didanosine or zidovudine). Read More

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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

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Barraquer-Simons syndrome in systemic lupus erythematosus: A case report.

Clin Case Rep 2021 Nov 22;9(11):e05132. Epub 2021 Nov 22.

Department of Internal Medicine Tribhuvan University Teaching Hospital Kathmandu Nepal.

Barraquer-Simons syndrome is a rare entity characterized by progressive loss of subcutaneous tissue in the face and/or upper half of the body and can be associated with autoimmune conditions such as systemic lupus erythematosus. Close long-term follow-up is required to identify metabolic disturbances, potentially life-threatening renal problems, and other associated diseases. Read More

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November 2021

Two Decades after Mandibuloacral Dysplasia Discovery: Additional Cases and Comprehensive View of Disease Characteristics.

Genes (Basel) 2021 09 26;12(10). Epub 2021 Sep 26.

Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria 21561, Egypt.

Pathogenic variants in the gene cause a group of heterogeneous genetic disorders, called laminopathies. In particular, homozygous or compound heterozygous variants in have been associated with "mandibuloacral dysplasia type A" (MADA), an autosomal recessive disorder, characterized by mandibular hypoplasia, growth retardation mainly postnatal, pigmentary skin changes, progressive osteolysis of the distal phalanges and/or clavicles, and partial lipodystrophy. The detailed characteristics of this multisystemic disease have yet to be specified due to its rarity and the limited number of cases described. Read More

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September 2021

A novel homozygous synonymous variant further expands the phenotypic spectrum of POLR3A-related pathologies.

Am J Med Genet A 2022 01 5;188(1):216-223. Epub 2021 Oct 5.

Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Pathogenic biallelic variants in POL3RA have been associated with different disorders characterized by progressive neurological deterioration. These include the 4H leukodystrophy syndrome (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) and adolescent-onset progressive spastic ataxia, as well as Wiedemann-Rautenstrauch syndrome (WRS), a recognizable neonatal progeroid syndrome. The phenotypic differences between these disorders are thought to occur mainly due to different functional effects of underlying POLR3A variants. Read More

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January 2022

Systematising Pharmacovigilance Engagement of Patients, Healthcare Professionals and Regulators: A Practical Decision Guide Derived from the International Risk Governance Framework for Engagement Events and Discourse.

Drug Saf 2021 11 15;44(11):1193-1208. Epub 2021 Sep 15.

Team Pharmacoepidemiology, Bordeaux University, INSERM, U1219 BPH Research Center, Bordeaux, France.

Introduction: Input from patients and healthcare professionals to regulatory assessments is essential for benefit-risk management of medicines. How to best obtain input in different risk scenarios is uncertain.

Objectives: The objective of this study was to investigate whether the International Risk Governance Council (IRGC) Framework is applicable to pharmacovigilance and can guide selecting engagement mechanisms for optimising stakeholder input. Read More

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November 2021

A De Novo Gene S90L Mutation in a Progressive Tetraparesis with Urinary Dysfunction and Corpus Callosum Involvement.

J Pediatr Genet 2021 Sep 8;10(3):253-258. Epub 2020 Jul 8.

Child Development Centre, Pediatric Hospital, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.

A Silver syndrome is a rare autosomal dominant spastic paraparesis in which spasticity of the lower limbs is accompanied by amyotrophy of the small hand muscles. The causative gene is the Berardinelli-Seip congenital lipodystrophy 2 ( , which is related to a spectrum of neurological phenotypes. In the current study, we presented a 14-year-old male with a slowly progressive spastic paraparesis with urinary incontinence that later on exhibited atrophy and weakness in the thenar and dorsal interosseous muscles. Read More

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September 2021

Severe onset of inflammatory myositis in a child: think to paraneoplastic myositis.

Ital J Pediatr 2021 Jul 1;47(1):146. Epub 2021 Jul 1.

University of Trieste, Via dell'Istria 65/1, Trieste, Italy.

Background: Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed. This report shows a case of severe CAM in a child. Read More

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Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database.

Sci Rep 2021 06 14;11(1):12438. Epub 2021 Jun 14.

Department of Pharmacy, Chongqing Health Center for Women and Children, Chongqing, 400021, China.

This current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. Read More

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Adipocyte-Specific Deletion of Lamin A/C Largely Models Human Familial Partial Lipodystrophy Type 2.

Diabetes 2021 09 4;70(9):1970-1984. Epub 2021 Jun 4.

Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI

Mechanisms by which autosomal recessive mutations in cause familial partial lipodystrophy type 2 (FPLD2) are poorly understood. To investigate the function of lamin A/C in adipose tissue, we created mice with an adipocyte-specific loss of ( ). Although mice develop and maintain adipose tissues in early postnatal life, they show a striking and progressive loss of white and brown adipose tissues as they approach sexual maturity. Read More

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September 2021

Celia's Encephalopathy (-Gene-Related): Current Understanding.

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Seipin, encoded by the gene, is a protein that in humans is expressed mainly in the central nervous system. Uniquely, certain variants in can cause both generalized congenital lipodystrophy type 2, upper and/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia's encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c. Read More

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Effects of Metreleptin on Patient Outcomes and Quality of Life in Generalized and Partial Lipodystrophy.

J Endocr Soc 2021 Apr 16;5(4):bvab019. Epub 2021 Feb 16.

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Generalized and partial lipodystrophy are rare and complex diseases with progressive clinical and humanistic burdens stemming from selective absence of subcutaneous adipose tissue, which causes reduced energy storage capacity and a deficiency of adipokines such as leptin. Treatment options were limited before leptin replacement therapy (metreleptin) became available. This retrospective study evaluates both clinical and humanistic consequences of the disease and treatment. Read More

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Ube2i deletion in adipocytes causes lipoatrophy in mice.

Mol Metab 2021 06 24;48:101221. Epub 2021 Mar 24.

Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, Houston, TX, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA. Electronic address:

Objective: White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosis and insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. Read More

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Protein Arginine Methyltransferase PRMT5 Regulates Fatty Acid Metabolism and Lipid Droplet Biogenesis in White Adipose Tissues.

Adv Sci (Weinh) 2020 Dec 16;7(23):2002602. Epub 2020 Oct 16.

Department of Animal Sciences Purdue University West Lafayette IN 47907 USA.

The protein arginine methyltransferase 5 (PRMT5) is an emerging regulator of cancer and stem cells including adipogenic progenitors. Here, a new physiological role of PRMT5 in adipocytes and systemic metabolism is reported. Conditional knockout mice were generated to ablate the gene specifically in adipocytes (Prmt5). Read More

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December 2020

Metreleptin for the treatment of progressive encephalopathy with/without lipodystrophy (PELD) in a child with progressive myoclonic epilepsy: a case report.

Ital J Pediatr 2020 Oct 24;46(1):158. Epub 2020 Oct 24.

Unit of Endocrinology, Bambino Gesù Children's Hospital, Rome, Italy.

Background: A number of genetic syndromes associated with variants in the BSCL2/seipin gene have been identified. Variants that cause skipping of exon 7 are associated with progressive encephalopathy with/without lipodystrophy (PELD), which is characterized by the development of progressive myoclonic epilepsy at a young age, severe progressive neurological impairment, and early death, often in childhood. Because the genetic basis of PELD is similar to that of congenital lipodystrophy type 2, we hypothesized that a patient with PELD may respond to treatments approved for other congenital lipodystrophic syndromes. Read More

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October 2020

Focus on progressive myoclonic epilepsy in Berardinelli-Seip syndrome.

Neurol Sci 2021 04 21;42(4):1597-1598. Epub 2020 Oct 21.

UETeM, CIMUS-IDIS, School of Medicine, University of Santiago de Compostela, Avda Barcelona s/n, 15782, Santiago de Compostela, Spain.

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Cardiovascular Involvement in Pediatric Laminopathies. Report of Six Patients and Literature Revision.

Front Pediatr 2020 24;8:374. Epub 2020 Jul 24.

The European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart-ERN GUARD-Heart, Pediatric Cardiology and Arrhythmia/Syncope Units, Bambino Gesù Children Hospital and Research Institute, Rome, Italy.

Lamin A/C () encodes for two nuclear intermediate filament proteins. Mutations in cause a highly heterogeneous group of diseases predominantly leading to muscular or cardiac disease, lipodystrophy syndromes, peripheral neuropathy, and accelerated aging disorders. Cardiac involvement includes progressive arrhythmias (brady/tachyarrhythmias, sudden cardiac death). Read More

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Focus on progressive myoclonic epilepsy in Berardinelli-Seip syndrome.

Neurol Sci 2020 Nov 21;41(11):3345-3348. Epub 2020 May 21.

Dipartimento di Medicina Molecolare e dello Sviluppo, Universita' degli Studi di Siena, viale Bracci 16, 53100, Siena, Italy.

Introduction: Berardinelli-Seip syndrome or congenital generalized lipodystrophy type 2 is a rare genetic disorder characterized by selective loss of subcutaneous adipose tissue associated with peripheral insulin resistance and its complications. Nonprogressive mental retardation, dystonia, ataxia, and pyramidal signs are commonly present, whereas epilepsy has only occasionally been observed.

Case Report: We report the case of two sisters, 11 and 18 years old respectively, with an overlapping clinical phenotype compatible with Berardinelli-Seip syndrome and progressive myoclonic epilepsy. Read More

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November 2020

Lipotransfer provides effective soft tissue replacement for acquired partial lipodystrophy.

BMJ Case Rep 2020 May 12;13(5). Epub 2020 May 12.

Division of Surgery & Interventional Science, University College London, London, UK.

We present a 48-year-old female patient who presented with features consistent with acquired partial lipodystrophy (APL) also known as 'Barraquer-Simons syndrome'. It is a rare disease characterised by a gradual and progressive onset of lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen and sparing the lower extremities. The resultant physical appearance can have significant psychosocial sequelae, further compounded by misdiagnosis and delay in recognition and management. Read More

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Human pluripotent stem cell-based models suggest preadipocyte senescence as a possible cause of metabolic complications of Werner and Bloom Syndromes.

Sci Rep 2020 05 4;10(1):7490. Epub 2020 May 4.

The University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.

Werner Syndrome (WS) and Bloom Syndrome (BS) are disorders of DNA damage repair caused by biallelic disruption of the WRN or BLM DNA helicases respectively. Both are commonly associated with insulin resistant diabetes, usually accompanied by dyslipidemia and fatty liver, as seen in lipodystrophies. In keeping with this, progressive reduction of subcutaneous adipose tissue is commonly observed. Read More

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Kosaki overgrowth syndrome: A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications.

Clin Genet 2020 07 4;98(1):19-31. Epub 2020 May 4.

Centre de Génétique et Centre de référence « Anomalies du Développement et Syndromes Malformatifs », Hôpital d'Enfants, Centre Hospitalier Universitaire de Dijon, Dijon, France.

Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p. Read More

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Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis.

Blood Purif 2020 19;49(4):457-467. Epub 2020 Mar 19.

Department of Nephrology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. Read More

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Congenital Generalized Lipoatrophy (Berardinelli-Seip Syndrome) Type 1: Description of Novel Homozygous Variants Showing the Highly Heterogeneous Presentation of the Disease.

Front Endocrinol (Lausanne) 2020 14;11:39. Epub 2020 Feb 14.

Obesity and Lipodystrophy Center at Endocrinology Unit, University Hospital of Pisa, Pisa, Italy.

Berardinelli-Seip congenital lipoatrophy (BSCL) is characterized by near total fat atrophy, associated with the progressive development of metabolic complications. BSCL type 1 (BSCL1) is caused by mutations in , encoding 1-acylglycerol-3phosphate-O-acyltransferase β (recently renamed lysophosphatidic acid acyltransferase beta), which catalyzes the transformation of lysophosphatidic acid in phosphatidic acid, the precursor of glycerophospholipids and triglycerides. BSCL1 is an autosomal recessive disease due to pathogenic variants leading to a depletion of triglycerides inside the adipose organ, and to a defective signaling of key elements involved in proper adipogenesis. Read More

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February 2021

Fibrodysplasia Ossificans Progressiva (FOP): A Segmental Progeroid Syndrome.

Front Endocrinol (Lausanne) 2019 10;10:908. Epub 2020 Jan 10.

Department of Orthopaedic Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Segmental progeroid syndromes are commonly represented by genetic conditions which recapitulate aspects of physiological aging by similar, disparate, or unknown mechanisms. Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease caused by mutations in the gene for ACVR1/ALK2 encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor, and results in the formation of extra-skeletal ossification and a constellation of others features, many of which resemble accelerated aging. The median estimated lifespan of individuals with FOP is approximately 56 years of age. Read More

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January 2020