Julliane Tamara Araújo de Melo Campos

Generalized lipodystrophies (GLs) are rare diseases characterized by a lack of body fat. When patients with a GL phenotype are referred with a presumptive diagnosis of congenital generalized lipodystrophy (CGL) but genetic testing for known pathogenic variants is negative, the diagnosis of acquired generalized lipodystrophy (AGL) becomes a more likely diagnosis. No single test confirms such a diagnosis, and it is crucial to recognize the similarities and differences between these diseases. We review the literature and report four GL cases from our lipodystrophy outpatient clinic, highlighting the main points for an accurate diagnosis. Similarities: phlebomegaly, umbilical scar protrusion, loss of Bichat’s fat pad, muscle hypertrophy, and hepatomegaly can occur in both. Cirrhosis can also arise, but in AGL, it occurs as a consequence of hepatic steatosis and also due to autoimmune hepatitis. Insulin resistance is frequent, and patients present acanthosis nigricans and acrochordons and may develop difficult-to-control diabetes and its complications, despite very high daily doses of insulin. Low HDL and hypertriglyceridemia are frequent and may progress to acute pancreatitis. Serum leptin levels are typically low and contribute to hyperphagia. Differences: AGL patients’ body fat loss occurs gradually in childhood or adolescence, whereas CGL patients are born with the characteristic phenotype. Evaluating photographs of AGL patients in the first years of life can provide evidence of this selective and gradual fat loss. Some AGL patients may have panniculitis (inflamed and painful subcutaneous nodules), with or without autoimmune diseases. In conclusion, recognizing both similarities and differences is crucial for making an accurate diagnosis and ensuring the most appropriate treatment.

1-Acylglycerol-3-phosphate O-acyltransferase (1-AGPAT) is an enzyme family composed of 11 isoforms. Notably, 1-AGPAT 2, the most studied isoform since its discovery, is a critical enzyme in the triglyceride synthesis pathway, converting lysophosphatidic acid to phosphatidic acid. In addition, AGPAT2 gene expression is shown to be essential for adipocyte development and maturation. Defects in AGPAT2 are responsible for significant pathophysiological alterations related to adipose tissue (AT). Pathogenic variants in this gene are the molecular etiology of Congenital Generalized Lipodystrophy type 1 (CGL1), in which fatty tissue is absent from birth. Metabolically, these individuals have several metabolic complications, including hypoleptinemia, hypoadiponectinemia, hyperglycemia, and hypertriglyceridemia. Furthermore, numerous AGPAT2 pathogenic variants that enormously affect the amino acid sequence, the tertiary structure of 1-AGPAT 2, and their transmembrane and functional domains were found in CGL1 patients. However, studies investigating the genotype–phenotype relationship in this disease are scarce. Here, we used bioinformatics tools to verify the effect of the main pathogenic variants reported in the AGPAT2 gene: c.366-588del, c.589-2A>G, c.646A>T, c.570C>A, c.369-372delGCTC, c.202C>T, c.514G>A, and c.144C>A in the 1-AGPAT 2 membrane topology. We also correlated the phenotype of CGL1 subjects harboring these variants to understand the genotype–phenotype relationship. We provided an integrative view of clinical, genetic, and metabolic features from CGL1 individuals, helping to understand the role of 1-AGPAT 2 in the pathogenesis of this rare disease. Data reviewed here highlight the importance of new molecular studies to improve our knowledge concerning clinical and genetic heterogeneity in CGL1.

Introduction and aim: Type 3 Familial Partial Lipodystrophy (FPLD3) is a rare metabolic disease related to pathogenic PPARG gene variants. FPLD3 is characterized by a loss of fatty tissue in the upper and lower limbs, hips, and face. FPLD3 pathophysiology is usually associated with metabolic comorbidities such as type 2 diabetes, insulin resistance, hypertriglyceridemia, and liver dysfunction. Here, we clinically and molecularly characterized FPLD3 patients harboring novel PPARG pathogenic variants. Materials and methods: Lipodystrophy-suspected patients were recruited by clinicians from an Endocrinology Reference Center. Clinical evaluation was performed, biological samples were collected for biochemical analysis, and DNA sequencing was performed to define the pathogenic variants associated with the lipodystrophic phenotype found in our clinically diagnosed FPLD subjects. Bioinformatics predictions were conducted to characterize the novel mutated PPARγ proteins. Results: We clinically described FPLD patients harboring two novel heterozygous PPARG variants in Brazil. Case 1 had the c.533T > C variant, which promotes the substitution of leucine to proline in position 178 (p.Leu178Pro), and cases 2 and 3 had the c.641 C > T variant, which results in the substitution of proline to leucine in the position 214 (p.Pro214Leu) at the PPARγ2 protein. These variants result in substantial conformational changes in the PPARγ2 protein. Conclusion: Two novel PPARG pathogenic variants related to FPLD3 were identified in a Brazilian FPLD cohort. These data will provide new epidemiologic data concerning FPLD3 and help understand the genotype-phenotype relationships related to the PPARG gene.

A Síndrome de Berardinelli-Seip (SBS) é uma rara doença genética autossômica recessiva, de alta prevalência no Rio Grande do Norte (RN), Brasil. O presente trabalho objetivou relatar a experiência dos acadêmicos de enfermagem, nutrição, psicologia e fisioterapia da Faculdade de Ciências da Saúde do Trairi (FACISA) durante ações multiprofissionais que englobavam pais e pessoas com a SBS no RN. Nesse projeto, foram realizadas orientações sobre alimentação saudável; escuta ativa para a compreensão do convívio social das pessoas com SBS; divulgações de materiais didáticos previamente produzidos; alongamento e relaxamento; e apresentações teatrais sobre a morfofisiologia e genética da SBS. Por meio desse projeto, tem sido possível propagar os conhecimentos sobre a SBS para a comunidade norte-rio-grandense que, em sua maioria, desconhece essa lipodistrofia tão prevalente na região. Adicionalmente, mudanças comportamentais mediadas por intervenções sistematizadas junto às famílias foram promovidas, melhorando a qualidade da assistência ofertada às pessoas com a SBS.

Background: Although rare, the rates of diagnosis of male breast cancer (MBC) have been increasing over the years, and it can be quite aggressive in the male organism. Some strategies such as health education disseminating knowledge about MBC can be essential for early discovery and finding better prognosis. Objective: Protocol to map the available evidence of health education approaches on MBC. Methods: A scoping review on health education on MBC will be carried out in Latin American and Caribbean Literature on Health Sciences (LILACS), Web of Science, Scopus, Scielo, Online System of Literature Search and Analysis Medical (MEDLINE), Embase, Virtual Health Library (VHL). Two independent reviewers will perform screening, data extraction, and risk of bias assessment through the Joanna Briggs Institute (JBI) Critical Assessment Checklist. For the quality of evidence, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Analysis will be used. Results: The results of this review will be published in a peer-reviewed journal. Conclusions: This scoping review will provide evidence of how health education on MBC is being addressed in health systems. Evidence can help healthcare professionals and patients recognize the most effective educational inventions in disseminating knowledge and preventing MBC.

Os Cursos de Férias de Morfofisiologia Humana têm sido realizados desde 2012 para estudantes do ensino médio das escolas públicas do Trairi, no estado do Rio Grande do Norte. O presente trabalho objetivou demonstrar os seus resultados positivos no auxílio à educação. Métodos criativos, participativos e inovadores foram utilizados, a partir do desenvolvimento de jogos, dinâmicas e peça teatral. Foram aplicados questionários aos participantes para avaliar quais temas os alunos gostariam de conhecer durante o curso, e o método empregado. Na edição de 2017, participaram 32 alunos, os quais demonstraram preferências em estudar o funcionamento do coração, do cérebro, das células e tecidos. A maioria avaliou como “muito bom” (> 70%) os itens: ambiente do laboratório, incentivo à criatividade, desempenho dos monitores e metodologia do curso. Esses cursos estimularam o desenvolvimento de competências e habilidades dos estudantes, contribuindo para o desenvolvimento social e o espírito crítico na formação do indivíduo.

Background: Congenital Generalized Lipodystrophy (CGL) is an ultra-rare disease characterized by metabolic disorders. However, the evaluation of functional exercise capacity, cardiovascular (CV) response to exercise, and peripheral arterial disease (PAD) in CGL is scarce. Here we evaluated the performance and CV response to exercise and their association with PAD in CGL compared to healthy individuals. Methods: Twelve CGL and 12 healthy subjects matched for age and gender were included. Functional exercise capacity, CV response, and PAD were measured using the six-minute walk test (6MWT) and ankle-brachial index (ABI), respectively. Results: At baseline, CGL subjects showed reduced predicted walked distance (6MWD) (p = 0.009) and increased heart rate (HR), systolic (SBP), and diastolic (DBP) pressures compared to healthy subjects (p < 0.05). Most CGL subjects presented normal ABI values (1.0 ≤ ABI ≤ 1.4). Only 25% (n = 3) had ABI ≤ 0.9. CGL subjects did not present changes in ABI and blood pressure 12 months after metreleptin (MLP) replacement, but they walked a greater 6MWD than baseline (p = 0.04). Further, 6MWD and right ABI measurements were positively correlated in CGL subjects (p = 0.03). Right ABI negatively correlated with glucose, triglycerides, and VLDL-c (p < 0.05). Conclusions: We observed that CGL subjects had lower functional exercise capacity and higher cardiovascular effort for similar performance of 6MWT, suggesting that strategies for decreasing exercise effort in this population should be essential. Furthermore, better physical performance was associated with high ABI in CGL. Additional studies are needed to clarify leptin's role in preserving functional exercise capacity in CGL.

O gene MFN2 codifica a proteína mitofusina 2. Uma variante patogênica pontual na sequência nucleotídica deste gene resulta na rara doença mitocondrial conhecida como Lipomatose Simétrica Múltipla (LSM). A LSM caracteriza-se fenotipicamente pelo desenvolvimento de lipomas benignos principalmente nas regiões supraclavicular, interescapular e pescoço.

Classical and progeroid congenital lipodystrophies are a collection of rare diseases displaying a large genetic heterogeneity. They occur due to pathogenic variants in genes associated with adipogenesis, DNA repair pathways, and genome stability. Subjects with lipodystrophy exhibit an impairment in the homeostasis of subcutaneous white adipose tissue (sWAT), resulting in low leptin and adiponectin levels, insulin resistance (IR), diabetes, dyslipidemia, ectopic fat deposition, inflammation, mitochondrial and endoplasmic reticulum commitments, among others. However, how pathogenic variants in adipogenesis-related genes modulate DNA repair in some classical congenital lipodystrophies has not been elucidated. In the same way, no data is clarifying how pathogenic variants in DNA repair genes result in sWAT loss in different types of progeroid lipodystrophies. This review will concentrate on the main molecular findings to understand the link between DNA damage/repair and adipogenesis in human and animal models of congenital lipodystrophies. We will focus on classical and progeroid congenital lipodystrophies directly or indirectly related to DNA repair pathways, highlighting the role of DNA repair-related proteins in maintaining sWAT homeostasis.