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2.
Rev. cuba. endocrinol ; 33(1)abr. 2022.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1408268

RESUMO

Introducción: La lipodistrofia congénita de Berardinelli-Seip es un síndrome genético autosómico recesivo, caracterizado por la ausencia generalizada del tejido adiposo, el déficit de leptina y las alteraciones metabólicas incluidas la resistencia a la insulina, la esteatohepatitis y la hipertrigliceridemia. Objetivo: Definir los diferentes espectros clínicos y fisiopatológicos del síndrome y su relación con el fenotipo definiendo las estrategias terapéuticas actuales. Métodos: Se realizó una búsqueda bibliográfica no sistemática en las bases de datos Science Direct, EMBASE, LILACS, Redalyc, SciELO y PubMed. Los criterios de inclusión fueron publicaciones en inglés, portugués o español, en las que el título y las palabras clave, abordaban el tema planteado con una vigencia de 10 años. Se obtuvieron 50 artículos relacionados con el síndrome, de los cuales 30 fueron seleccionados para su revisión. Conclusiones: El diagnóstico de la enfermedad es principalmente clínico. Se establece en presencia de tres criterios mayores o la combinación de dos mayores con dos menores y/o por la identificación de variantes patogénicas por medio del estudio genético y molecular. La dieta y el ejercicio conjuntamente con la administración de la metreleptina son pilares fundamentales en el manejo de estos pacientes. El reconocimiento temprano del síndrome es esencial para prevenir las complicaciones, y brindar asesoría genética y reproductiva a los pacientes y familiares(AU)


Introduction: Berardinelli-Seip congenital lipodystrophy is an autosomal recessive genetic syndrome, characterized by the general absence of adipose tissue, leptin deficiency and metabolic alterations including insulin resistance, steatohepatitis and hypertriglyceridemia. Objective: To present the different clinical and pathophysiological spectra of the syndrome, its relationship with the phenotype, defining the current therapeutic strategies. Methods: A non-systematic bibliographic search was carried out in Science Direct, EMBASE, LILACS, Redalyc, SciELO and PubMed databases. The inclusion criteria were publications in English, Portuguese and Spanish, in which the title and keywords included information pertinent to the stated objective with a periodicity of 10 years, 50 articles were retrieved, and 30 of them were selected. Conclusions: The diagnosis of the disease is mainly clinical. It is established in the presence of three major criteria or the combination of two major and two minor criteria and/or by the identification of pathogenic variants through genetic and molecular studies. Diet and exercise together with the administration of metreleptin are fundamental pillars in the management of these patients. Early recognition of the syndrome is essential to prevent complications, allowing genetic and reproductive counseling to be provided to patients and their families(AU)


Assuntos
Humanos , Síndrome Metabólica/prevenção & controle , Lipodistrofia Generalizada Congênita/fisiopatologia , Resistência à Insulina , Literatura de Revisão como Assunto , Bases de Dados Bibliográficas , Estratégias de Saúde
3.
Mol Metab ; 36: 100971, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32246911

RESUMO

OBJECTIVE: Understanding the mechanisms that control brown adipose tissue (BAT) mass and functionality is crucial for our understanding of how the disruption of energy homeostasis leads to obesity. Bernerdinali Seip Congenital Lipodystrophy (BSCL) type 2 (BSCL2, a.k.a. SEIPIN), a lipodystrophy-associated protein, has been shown to not be required for brown adipogenesis, but it has been shown to be essential for perinatal BAT development. However, its role in mature BAT maintenance and thermogenic programing remains poorly understood. METHODS: We subjected Bscl2f/f and Bscl2UCP1-BKO (BKO) mice with a brown adipose-specific loss of BSCL2 through UCP1 promoter-driven Cre to environmental, pharmacological and diet interventions to challenge BAT functionality and reprogramming. We carried out physiological, molecular and transcriptomic analyses of BAT. RESULTS: The deletion of BSCL2 in mature brown adipocytes increased sympathetic nervous system-independent cAMP/protein kinase A (PKA) signaling in BAT. Such activation reduced BAT triglyceride content and mass and was sufficient to reduce plasma triglyceride, but not enough to combat thermoneutral and high fat diet-induced obesity. Surprisingly, BKO mice displayed an impaired response to acute and chronic cold challenges despite cAMP/PKA activation. When subjected to chronic cold exposure or the administration of a ß3-adrenergic agonist, CL 316,243, BKO mice failed to induce BAT recruitment and underwent dramatic brown adipocyte loss. Transcriptomic analysis revealed pathological BAT remodeling with inflammation and fibrosis, which was further exacerbated by a chronic thermogenic challenge in BKO mice. Mechanistically, we found abnormal mitochondrial shapes and function in BAT of BKO mice housed at 21 °C; as well as mitochondrial DNA depletion and necroptotic-mediated brown adipocyte death after chronic thermogenic insult. CONCLUSION: BSCL2-mediated lipid catabolism within BAT is crucial for mature brown adipocyte function and survival both during times of activation and quiescence. BSCL2 is an important regulator of mature brown adipocyte mitochondrial metabolism, necroptosis and thus adaptive thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Subunidades gama da Proteína de Ligação ao GTP/metabolismo , Lipodistrofia Generalizada Congênita/metabolismo , Adipócitos Marrons/metabolismo , Adipogenia , Tecido Adiposo Marrom/fisiologia , Animais , Diferenciação Celular/genética , Feminino , Subunidades gama da Proteína de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Homeostase , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Lipídeos/fisiologia , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipólise/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Obesidade/metabolismo , Transdução de Sinais/genética , Termogênese , Triglicerídeos/metabolismo
4.
Arq Bras Cardiol ; 114(2): 305-312, 2020 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32215503

RESUMO

Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.


Assuntos
Cardiomegalia/etiologia , Cardiomiopatia Hipertrófica/etiologia , Lipodistrofia Generalizada Congênita/complicações , Lipodistrofia Parcial Familiar/complicações , Tecido Adiposo/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/fisiopatologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda , Lipodistrofia Generalizada Congênita/diagnóstico por imagem , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Parcial Familiar/diagnóstico por imagem , Lipodistrofia Parcial Familiar/fisiopatologia , Imageamento por Ressonância Magnética
5.
Arq. bras. cardiol ; 114(2): 305-312, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1088853

RESUMO

Abstract Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.


Resumo A lipodistrofia familiar é uma condição genética rara na qual indivíduos apresentam, além das alterações metabólicas e de depósitos de gordura físicos, um tipo de cardiomiopatia pouco estudada. Muitos dos pacientes desenvolvem alterações cardiovasculares, sendo a mais comumente reportada em literatura, a expressão de um tipo de cardiomiopatia hipertrófica. Este artigo, apresentado como uma revisão bibliográfica, revisa os aspectos clínicos e de imagem cardiovascular neste cenário de cardiomiopatia em doença metabólica rara, com base nas últimas evidências científicas publicadas na área. Apesar da frequente associação de lipodistrofia congênita e hipertrofia ventricular descrita em literatura, os mecanismos fisiopatológicos desta cardiomiopatia ainda não estão definitivamente elucidados, e novas informações do aspecto morfológico cardíaco surgem à égide de recentes e avançados métodos de imagem como a ressonância cardíaca magnética.


Assuntos
Humanos , Cardiomiopatia Hipertrófica/etiologia , Cardiomegalia/etiologia , Lipodistrofia Parcial Familiar/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Tecido Adiposo/fisiopatologia , Hipertrofia Ventricular Esquerda , Cardiomegalia/fisiopatologia , Cardiomegalia/diagnóstico por imagem , Lipodistrofia Generalizada Congênita/complicações , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Generalizada Congênita/diagnóstico por imagem , Lipodistrofia Parcial Familiar/fisiopatologia , Lipodistrofia Parcial Familiar/diagnóstico por imagem
6.
Epileptic Disord ; 21(1): 117-121, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30767895

RESUMO

Berardinelli-Seip syndrome, or congenital generalized lipodystrophy type 2 (CGL2), is characterized by a lack of subcutaneous adipose tissue and precocious metabolic syndrome with insulin resistance, resulting in diabetes, dyslipidaemia, hepatic steatosis, cardiomyopathy, and acanthosis nigricans. Most reported mutations are associated with mild, non-progressive neurological impairment. We describe the clinical and EEG data of a patient with progressive myoclonus epilepsy (PME), CGL2, and progressive neurological impairment, carrying a homozygous BSCL2 nonsense mutation. The patient had epilepsy onset at the age of two, characterized by monthly generalized tonic-clonic seizures. By the age of three, he presented with drug-resistant ongoing myoclonic absence seizures, photosensitivity, progressive neurological degeneration, and moderate cognitive delay. Molecular analysis of the BSCL2 gene yielded a homozygous c.(1076dupC) p.(Glu360*) mutation. Application of a vagus nerve stimulator led to temporary improvement in seizure frequency, general neurological condition, and EEG background activity. Specific BSCL2 mutations may lead to a peculiar CGL2 phenotype characterized by PME and progressive neurodegeneration. Application of a vagus nerve stimulator, rarely used for PMEs, may prove beneficial, if only temporarily, for both seizure frequency and general neurological condition.


Assuntos
Subunidades gama da Proteína de Ligação ao GTP/genética , Lipodistrofia Generalizada Congênita , Epilepsias Mioclônicas Progressivas , Pré-Escolar , Eletroencefalografia , Humanos , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Generalizada Congênita/terapia , Masculino , Epilepsias Mioclônicas Progressivas/genética , Epilepsias Mioclônicas Progressivas/fisiopatologia , Epilepsias Mioclônicas Progressivas/terapia , Estimulação do Nervo Vago
7.
Respir Res ; 19(1): 173, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208912

RESUMO

BACKGROUND: Berardinelli-Seip Congenital Generalized Lipodystrophy (BSCL) is an ultra-rare metabolic disease characterized by hypertriglyceridemia, hyperinsulinemia, hyperglycemia, hypoleptinemia, and diabetes mellitus. Although cardiovascular disturbances have been observed in BSCL patients, there are no studies regarding the Respiratory Muscle Strength (RMS) in this type of lipodystrophy. This study aimed to evaluate RMS in BSCL subjects compared with healthy subjects. METHODS: Eleven individuals with BSCL and 11 healthy subjects matched for age and gender were included in this study. The Maximum Inspiratory Pressure (MIP), Maximum Expiratory Pressure (MEP), and Peripheral Muscle Strength (PMS) were measured for three consecutive years. BSCL subjects were compared to healthy individuals for MIP, MEP, and PMS. Correlations between PMS and MIP were also analyzed. The genetic diagnosis was performed, and sociodemographic and anthropometric data were also collected. RESULTS: BSCL subjects showed significantly lower values for MIP and MEP (p <  0.0001 and p = 0.0002, respectively) in comparison to healthy subjects, but no changes in handgrip strength (p = 0.15). Additionally, we did not observe changes in MIP, MEP, and PMS two years after the first analysis, showing maintenance of respiratory dysfunction in BSCL subjects (p = 0.05; p = 0.45; p = 0.99). PMS and MIP were not correlated in these subjects (r = 0.56; p = 0.18). CONCLUSION: BSCL subjects showed lower respiratory muscle strength when compared with healthy subjects; however, PMS was not altered. These findings were maintained at similar levels during the two years of evaluation. Our data reveal the first association of BSCL with the development of respiratory muscle weakness.


Assuntos
Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/fisiopatologia , Força Muscular/fisiologia , Músculos Respiratórios/fisiopatologia , Adulto , Estudos Transversais , Feminino , Humanos , Leptina/análogos & derivados , Leptina/farmacologia , Leptina/uso terapêutico , Lipodistrofia Generalizada Congênita/tratamento farmacológico , Estudos Longitudinais , Masculino , Pressões Respiratórias Máximas/métodos , Força Muscular/efeitos dos fármacos , Músculos Respiratórios/efeitos dos fármacos , Adulto Jovem
8.
PLoS One ; 13(6): e0197784, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29864145

RESUMO

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease characterized by the almost complete absence of adipose tissue. Due to a strong founder effect that resulted in a higher prevalence of BSCL in Rio Grande do Norte (RN), a state in northeastern Brazil, it has been essential that health professionals develop knowledge about this disease. Nurses are often the first point of contact with patients during health care assistance. The purpose of this study was to investigate the knowledge of these professionals about BSCL in two main hospitals in RN state. A questionnaire was applied to 199 nurses working in the Hospital Regional Mariano Coelho-HRMC (Regional Hospital Mariano Coelho), in Currais Novos-RN, and in the Hospital Universitário Onofre Lopes-HUOL (University Hospital Onofre Lopes), in Natal-RN. This study showed that most nursing professionals do not know about the disease, although they have already received patients with BSCL in those hospitals. The nurses from HRMC and HUOL lacked knowledge of BSCL and the healthcare of these patients requires immediate improvement. Significant efforts are required to close the gap between current and needed practice patterns.


Assuntos
Tecido Adiposo/fisiopatologia , Lipodistrofia Generalizada Congênita/epidemiologia , Lipodistrofia Generalizada Congênita/genética , Enfermeiras e Enfermeiros , Adulto , Brasil/epidemiologia , Educação em Enfermagem , Feminino , Efeito Fundador , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lipodistrofia Generalizada Congênita/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
9.
J Coll Physicians Surg Pak ; 28(5): 406-408, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29690976

RESUMO

Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is a rare genetic disorder caused by dysregulation of glycemic and lipid metabolism. We report five BSCL cases with typical clinical pictures and complications. These, to the best of our knowledge, represent the first case series from Pakistan. BSCL is characterized by marked atrophy of adipose tissue, acromegaly, acanthosis nigricans and tall stature. We could not perform genetics studies in any patient owing to non-availability of genetic laboratory in Pakistan. All the cases presented hypertriglyceridemia. One case developed hyperinsulinism controlled with metformin. There is no curative treatment and the current approach is low-fat diet and management of insulin resistance and diabetes. Recently published studies showed that leptin-replacement therapy is promising in the metabolic correction of complications of BSCL. This highlights the importance of further research in BSCL treatment.


Assuntos
Lipodistrofia Generalizada Congênita/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Resistência à Insulina , Lipodistrofia Generalizada Congênita/fisiopatologia , Masculino , Doenças Raras
10.
Cien Saude Colet ; 23(2): 389-398, 2018 Feb.
Artigo em Português, Inglês | MEDLINE | ID: mdl-29412397

RESUMO

This paper analyzes the experience of people living with the Berardinelli-Seip Syndrome in the Brazilian Northeast. This qualitative study was developed with eleven informants, namely, nine people living with the syndrome and two mothers. Information was gathered using participant observation, social characterization and semi-structured interviews. Data were analyzed by means of a thematic coding technique. Two categories emerged: (1) 'the secret is to shut your mouth': food management in daily life; and (2) 'Ah, is it a transvestite?' body, gender, and masculinization. We concluded that, in the experience of the informants, their negotiations and creativity translated into strategies for food management that integrated tastes, values, habits, biomedical prescriptions and pleasures involved in commensality situations. Regarding corporeality, it has been shown that representations and experiences with the body show gender inequalities, insofar as women become privileged targets of stigmas, prejudices and discrimination in adult life.


O artigo analisa a experiência de pessoas que vivem com a Síndrome de Berardinelli-Seip no Nordeste brasileiro. Este estudo qualitativo foi desenvolvido com onze interlocutores, sendo nove pessoas vivendo com a síndrome e duas mães. Para coligir as informações, utilizaram-se observação participante, caracterização social e entrevistas semiestruturadas. Os dados foram analisados por meio da técnica de codificação temática. Emergiram duas categorias: (1) 'o segredo é fechar a boca': gerenciamento da alimentação na vida cotidiana; e (2) 'ah, é uma travesti?' Corpo, gênero e masculinização. Concluiu-se que na experiência dos interlocutores seus agenciamentos e criatividade se traduziram em estratégias para gerenciamento da alimentação que integravam gostos, valores, hábitos, prescrições biomédicas e prazeres envolvidos em situações de comensalidade. No que tange à corporeidade, evidenciou-se que as representações e as experiências com o corpo apresentam desigualdades de gênero, na medida em que a mulher passa a ser alvo privilegiado de estigmas, preconceitos e discriminação na vida adulta.


Assuntos
Lipodistrofia Generalizada Congênita/fisiopatologia , Discriminação Social , Estigma Social , Brasil , Feminino , Humanos , Entrevistas como Assunto , Lipodistrofia Generalizada Congênita/psicologia , Masculino
11.
Ciênc. Saúde Colet. (Impr.) ; 23(2): 389-398, Fev. 2018.
Artigo em Português | LILACS | ID: biblio-890522

RESUMO

Resumo O artigo analisa a experiência de pessoas que vivem com a Síndrome de Berardinelli-Seip no Nordeste brasileiro. Este estudo qualitativo foi desenvolvido com onze interlocutores, sendo nove pessoas vivendo com a síndrome e duas mães. Para coligir as informações, utilizaram-se observação participante, caracterização social e entrevistas semiestruturadas. Os dados foram analisados por meio da técnica de codificação temática. Emergiram duas categorias: (1) 'o segredo é fechar a boca': gerenciamento da alimentação na vida cotidiana; e (2) 'ah, é uma travesti?' Corpo, gênero e masculinização. Concluiu-se que na experiência dos interlocutores seus agenciamentos e criatividade se traduziram em estratégias para gerenciamento da alimentação que integravam gostos, valores, hábitos, prescrições biomédicas e prazeres envolvidos em situações de comensalidade. No que tange à corporeidade, evidenciou-se que as representações e as experiências com o corpo apresentam desigualdades de gênero, na medida em que a mulher passa a ser alvo privilegiado de estigmas, preconceitos e discriminação na vida adulta.


Abstract This paper analyzes the experience of people living with the Berardinelli-Seip Syndrome in the Brazilian Northeast. This qualitative study was developed with eleven informants, namely, nine people living with the syndrome and two mothers. Information was gathered using participant observation, social characterization and semi-structured interviews. Data were analyzed by means of a thematic coding technique. Two categories emerged: (1) 'the secret is to shut your mouth': food management in daily life; and (2) 'Ah, is it a transvestite?' body, gender, and masculinization. We concluded that, in the experience of the informants, their negotiations and creativity translated into strategies for food management that integrated tastes, values, habits, biomedical prescriptions and pleasures involved in commensality situations. Regarding corporeality, it has been shown that representations and experiences with the body show gender inequalities, insofar as women become privileged targets of stigmas, prejudices and discrimination in adult life.


Assuntos
Humanos , Masculino , Feminino , Lipodistrofia Generalizada Congênita/fisiopatologia , Estigma Social , Discriminação Social , Brasil , Entrevistas como Assunto , Lipodistrofia Generalizada Congênita/psicologia
12.
BMC Cardiovasc Disord ; 18(1): 6, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329523

RESUMO

BACKGROUND: Metabolic abnormalities in congenital generalized lipodystrophy (CGL) are associated with microvascular complications. However, the evaluation of different types of neuropathy in these patients, including the commitment of cardiovascular autonomic modulation, is scarce. The objective of the present study was to determine the prevalence of cardiovascular autonomic neuropathy (CAN) in patients with CGL compared with individuals with type 1 diabetes and healthy subjects. METHODS: Ten patients with CGL, 20 patients with type 1 diabetes and 20 healthy subjects were included in the study. Controls were paired 1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was analyzed using cardiovascular autonomic reflex tests, including postural hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15) coefficients, and spectral analysis of the HRV, determining very low (VLF), low (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as the presence of at least two altered tests. RESULTS: CAN was detected in 40% of the CGL patients, 5% in type 1 diabetes patients and was absent in healthy individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels of 30/15 and VAL in CGL vs. healthy individuals. A significant positive correlation was observed between leptin and 30/15 coefficient (r = 0.396; p = 0.036) after adjusting for insulin resistance and triglycerides. Autonomic cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and albumin/creatinine ratio in CGL cases. CONCLUSIONS: We observed a high prevalence of CAN in young patients with CGL, suggesting that insulin resistance, hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN development. Additional studies are needed to evaluate the role of leptinemia in the physiopathogenesis of the condition.


Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/inervação , Frequência Cardíaca , Lipodistrofia Generalizada Congênita/fisiopatologia , Adolescente , Adulto , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/epidemiologia , Biomarcadores/sangue , Glicemia/metabolismo , Brasil/epidemiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Criança , Creatinina/sangue , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/epidemiologia , Masculino , Prevalência , Albumina Sérica Humana/análise , Triglicerídeos/sangue
13.
J Clin Densitom ; 21(1): 61-67, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27894728

RESUMO

Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty storing lipid in adipocytes, low body fat, hypoleptinemia, and hyperinsulinemia. We report here laboratory, bone mineral density (BMD), and bone mineral content findings of 21 patients (24.1 ± 8.4 yr old, 14 females, 18 diabetics, 5.3% total body fat) with BSCL. The mean leptin was very low (0.91 ± 0.42 ng/mL), and the mean values of the Z-scores for all studied sites were positive, except for the 33% radius (Z-score -0.5 standard deviation [SD]). Twelve patients (57.1%) had a BMD Z-score higher than +2.5 SD in at least 1 site. There was no significant difference in the Z-scores between males and females. None of type 1 (AGPAT2) patients had Z-scores higher than +2.5 SD, and these patients had a smaller Z-score of BMD total body (0.26 SD vs 1.90 SD, p = 0.022) and of bone mineral content (1.59 SD vs 3.3 SD, p = 0.032) than type 2 (seipin) patients. Insulin, as well as HOMAIR (homeostasis model assessment), correlated positively with the BMD of all sites, except for the 33% radius. Z-Scores on this site (33% radius) were the smallest of all. More than half of our patients with BSCL have BMD Z-scores higher than +2.5 SD on at least 1 site, and this increase is more pronounced in the trabecular sites and in type 2 patients.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Insulina/sangue , Leptina/sangue , Lipodistrofia Generalizada Congênita/diagnóstico por imagem , Lipodistrofia Generalizada Congênita/fisiopatologia , Aciltransferases/genética , Adolescente , Adulto , Osso Esponjoso/fisiopatologia , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Subunidades gama da Proteína de Ligação ao GTP/genética , Homeostase , Humanos , Resistência à Insulina , Lipodistrofia Generalizada Congênita/genética , Vértebras Lombares/diagnóstico por imagem , Masculino , Rádio (Anatomia)/diagnóstico por imagem , Adulto Jovem
14.
Am J Med Genet A ; 173(9): 2517-2521, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28686329

RESUMO

The LMNA gene contains 12 exons and encodes lamins A and C by alternative splicing within exon 10. While mutations in lamin A specific residues cause several diseases including lipodystrophy, progeria, muscular dystrophy, neuropathy, and cardiomyopathy, only three families with mutations in lamin C-specific residues are reported with cardiomyopathy, neuropathy, and muscular dystrophy so far. We now report two brothers with juvenile-onset generalized lipodystrophy due to a lamin C-specific mutation. The proband, a 23-year-old Caucasian male was reported to have generalized lipodystrophy at 3 weeks of age, developed diabetes, hypertriglyceridemia, hypertension and liver problems and died with complications of cirrhosis, and kidney failure. His younger brother, a 37-year-old Caucasian male developed generalized lipodystrophy around 2 years of age and was diagnosed with diabetes, hypertriglyceridemia, fatty liver, and hypertension at 36 years of age. Their father also died of end stage renal disease at age 52 years. Exome sequencing of the proband revealed an extremely rare missense heterozygous variant c.1711_1712CG>TC; p.(Arg571Ser) in LMNA which was confirmed by Sanger sequencing in both the patients. Interestingly, the mutation had no effect on mRNA splicing or relative expression of lamin A or C mRNA and protein in the lymphoblasts. Our observations suggest that mutant lamin C disrupts its interaction with other cellular proteins resulting in generalized lipodystrophy due to defective development and maintenance of adipose tissue.


Assuntos
Diabetes Mellitus/genética , Hipertrigliceridemia/genética , Lamina Tipo A/genética , Lipodistrofia Generalizada Congênita/genética , Adulto , Idade de Início , Processamento Alternativo , Diabetes Mellitus/fisiopatologia , Exoma/genética , Heterozigoto , Humanos , Hipertrigliceridemia/fisiopatologia , Lipodistrofia Generalizada Congênita/fisiopatologia , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Splicing de RNA/genética
15.
Rev. cuba. endocrinol ; 28(1): 1-7, Jan.-Apr. 2017. ilus
Artigo em Espanhol | LILACS | ID: biblio-901010

RESUMO

El síndrome Berardinelli es una enfermedad poco frecuente, con amplia heterogeneidad clínica y genética, clínicamente caracterizada por pérdida de tejido adiposo a nivel subcutáneo y de otros tejidos. Esta lipodistrofia generalizada congénita provoca hipertrofia muscular, asociada a trastornos endocrinos, con crecimiento acelerado durante la infancia, pubertad precoz e hiperglicemia. Está considerada una enfermedad metabólica rara, que se hereda de forma autosómico recesiva. En la actualidad se describen 4 variantes de este síndrome, con varios genes implicados. El objetivo de este trabajo es describir las características clínicas en una niña, en la cual su aspecto fenotípico recuerda este síndrome, por la lipodistrofia marcada y aumento de la musculatura desde la etapa de lactante, por lo cual se consideró necesaria la valoración en equipo multidisciplinario para su adecuado seguimiento y asesoramiento genético a sus familiares(AU)


Berardinelli syndrome is a rare disease, with broad clinical and genetic heterogeneity, and clinically characterized by loss of fatty tissue at subcutaneous level and of other tissues. This generalized congenital lipodystrophy causes muscle hypertrophy associated to endocrine disorders, accelerated growth at childhood, early puberty and hyperglycemia. It is considered as a rare metabolic disease and also recessive autosomal inheritance. Nowadays, four variants of the syndrome are described in which several gens are involved. The objective of this paper was to describe the clinical characteristics of a girl whose phenotypical aspect resembles this syndrome due to the marked lipodystrophy and increased musculature since her breastfeeding phase. Therefore, it was necessary to make an assessment by a multidisciplinary team for her adequate follow-up and the genetic counselling to her family(AU)


Assuntos
Humanos , Feminino , Pré-Escolar , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Parcial Familiar/epidemiologia
16.
Rev. cuba. endocrinol ; 28(1): 1-7, Jan.-Apr. 2017. ilus
Artigo em Espanhol | CUMED | ID: cum-73046

RESUMO

El síndrome Berardinelli es una enfermedad poco frecuente, con amplia heterogeneidad clínica y genética, clínicamente caracterizada por pérdida de tejido adiposo a nivel subcutáneo y de otros tejidos. Esta lipodistrofia generalizada congénita provoca hipertrofia muscular, asociada a trastornos endocrinos, con crecimiento acelerado durante la infancia, pubertad precoz e hiperglicemia. Está considerada una enfermedad metabólica rara, que se hereda de forma autosómico recesiva. En la actualidad se describen 4 variantes de este síndrome, con varios genes implicados. El objetivo de este trabajo es describir las características clínicas en una niña, en la cual su aspecto fenotípico recuerda este síndrome, por la lipodistrofia marcada y aumento de la musculatura desde la etapa de lactante, por lo cual se consideró necesaria la valoración en equipo multidisciplinario para su adecuado seguimiento y asesoramiento genético a sus familiares(AU)


Berardinelli syndrome is a rare disease, with broad clinical and genetic heterogeneity, and clinically characterized by loss of fatty tissue at subcutaneous level and of other tissues. This generalized congenital lipodystrophy causes muscle hypertrophy associated to endocrine disorders, accelerated growth at childhood, early puberty and hyperglycemia. It is considered as a rare metabolic disease and also recessive autosomal inheritance. Nowadays, four variants of the syndrome are described in which several gens are involved. The objective of this paper was to describe the clinical characteristics of a girl whose phenotypical aspect resembles this syndrome due to the marked lipodystrophy and increased musculature since her breastfeeding phase. Therefore, it was necessary to make an assessment by a multidisciplinary team for her adequate follow-up and the genetic counselling to her family(AU)


Assuntos
Humanos , Feminino , Pré-Escolar , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Parcial Familiar/epidemiologia
17.
Seizure ; 42: 1-6, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27632409

RESUMO

PURPOSE: A small case series with a neurodegenerative disorder involving central nervous system and related to Seipin mutations was recently reported. Herein we describe clinical and EEG features of three patients presenting with Progressive Myoclonus Epilepsy (PME) and Congenital Generalized Lipodystrophy type 2 (CGL2) related to novel Seipin mutations. METHODS: The EEG-clinical picture was evaluated at epilepsy onset and in the follow-up period. The molecular analysis of BSCL2, Laforin and Malin genes was performed to patients and/or their parents by Denaturing High Performance Liquid Chromatography and automated nucleotide sequencing. Skin specimens collected from a patient were processed for histochemical and ultrastructural analysis. RESULTS: The CGL2-PME syndrome co-segregated with two different BSCL2 genotypes: the homozygosity for c.782_783dupG involving exon 8 (two cases), or the compound heterozygosity for c.782_783dupG/c.828_829delAA (one case). Periodic-Acid Schiff positive osmiophilic material in the cytoplasm of fibrocytes and eccrine-gland cells were found in skin specimens. The lack of Lafora's bodies in skin specimens and the molecular analysis excluding mutations in Laforin and Malin genes ruled out Lafora disease. CONCLUSION: The spectrum of CGL2 associated to BSCL2 gene mutations may include PMEs. Selected mutations in BSCL2 gene seem to be related to PMEs in patients with CGL2 phenotype.


Assuntos
Encéfalo/fisiopatologia , Subunidades gama da Proteína de Ligação ao GTP/genética , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia Generalizada Congênita/fisiopatologia , Epilepsias Mioclônicas Progressivas/genética , Epilepsias Mioclônicas Progressivas/fisiopatologia , Encéfalo/diagnóstico por imagem , Proteínas de Transporte/genética , Criança , Diagnóstico Diferencial , Evolução Fatal , Feminino , Humanos , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/patologia , Masculino , Epilepsias Mioclônicas Progressivas/diagnóstico , Epilepsias Mioclônicas Progressivas/patologia , Proteínas Tirosina Fosfatases não Receptoras/genética , Pele/metabolismo , Pele/patologia , Ubiquitina-Proteína Ligases
18.
Hum Mol Genet ; 25(23): 5111-5125, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27638887

RESUMO

Hereditary spastic paraplegias (HSPs; SPG1-76 plus others) are length-dependent disorders affecting long corticospinal axons, and the most common autosomal dominant forms are caused by mutations in genes that encode the spastin (SPG4), atlastin-1 (SPG3A) and REEP1 (SPG31) proteins. These proteins bind one another and shape the tubular endoplasmic reticulum (ER) network throughout cells. They also are involved in lipid droplet formation, enlargement, or both in cells, though mechanisms remain unclear. Here we have identified evidence of partial lipoatrophy in Reep1 null mice in addition to prominent spastic paraparesis. Furthermore, Reep1-/- embryonic fibroblasts and neurons in the cerebral cortex both show lipid droplet abnormalities. The apparent partial lipodystrophy in Reep1 null mice, although less severe, is reminiscent of the lipoatrophy phenotype observed in the most common form of autosomal recessive lipodystrophy, Berardinelli-Seip congenital lipodystrophy. Berardinelli-Seip lipodystrophy is caused by autosomal recessive mutations in the BSCL2 gene that encodes an ER protein, seipin, that is also mutated in the autosomal dominant HSP SPG17 (Silver syndrome). Furthermore, REEP1 co-immunoprecipitates with seipin in cells. This strengthens the link between alterations in ER morphogenesis and lipid abnormalities, with important pathogenic implications for the most common forms of HSP.


Assuntos
Retículo Endoplasmático/genética , Lipodistrofia Generalizada Congênita/genética , Proteínas de Membrana Transportadoras/genética , Paraplegia Espástica Hereditária/genética , Animais , Axônios/metabolismo , Axônios/patologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Subunidades gama da Proteína de Ligação ao GTP , Proteínas Heterotriméricas de Ligação ao GTP/genética , Humanos , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Lipodistrofia Generalizada Congênita/metabolismo , Lipodistrofia Generalizada Congênita/fisiopatologia , Proteínas de Membrana Transportadoras/metabolismo , Camundongos , Camundongos Knockout , Morfogênese/genética , Mutação , Tratos Piramidais/metabolismo , Tratos Piramidais/patologia , Paraplegia Espástica Hereditária/metabolismo , Paraplegia Espástica Hereditária/fisiopatologia
19.
Eur J Med Genet ; 59(6-7): 320-4, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27167729

RESUMO

Congenital generalized lipodystrophy type 4 is an extremely rare autosomal recessive disorder. We report our clinical experience on two unrelated Turkish patients with congenital generalized lipodystrophy type 4. A 13-year-old girl (patient-1) presented with generalized lipodystrophy and myopathy. Further tests revealed ventricular and supraventricular arrhythmias, gastrointestinal dysmotility, atlantoaxial instability, lumbosacral scoliosis, and metabolic abnormalities associated with insulin resistance. A 16-year-old girl (patient-2) with congenital generalized lipodystrophy type 4 was previously reported. Here, we report on her long term clinical follow-up. She received several course of anti-arrhythmic treatments for catecholaminergic polymorphic ventricular tachycardia and rapid atrial fibrillation. An implantable cardioverter defibrillator was also placed. A homozygous PTRF mutation, c.259C > T (p.Gln87*), was identified in patient-1. Congenital generalized lipodystrophy type 4 was caused by homozygous PTRF c.481-482insGTGA (p.Lys161Serfs*41) mutation in patient-2. Our data indicate that patients with congenital generalized lipodystrophy type 4 should be meticulously evaluated for cardiac, neuromuscular, gastrointestinal and skeletal diseases, as well as metabolic abnormalities associated with insulin resistance.


Assuntos
Arritmias Cardíacas/genética , Resistência à Insulina/genética , Lipodistrofia Generalizada Congênita/genética , Proteínas de Ligação a RNA/genética , Adolescente , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/terapia , Feminino , Homozigoto , Humanos , Lipodistrofia Generalizada Congênita/fisiopatologia , Lipodistrofia Generalizada Congênita/terapia , Mutação , Linhagem , Taquicardia Ventricular/genética , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Turquia
20.
J Clin Endocrinol Metab ; 101(7): 2892-904, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27144934

RESUMO

CONTEXT: Mutations in PTRF encoding cavin-1 are responsible for congenital generalized lipodystrophy type 4 (CGL4) characterized by lipoatrophy, insulin resistance, dyslipidemia, and muscular dystrophy. Cavin-1 cooperates with caveolins to form the plasma membrane caveolae, which are involved in cellular trafficking and signalling and in lipid turnover. OBJECTIVE: We sought to identify PTRF mutations in patients with CGL and to determine their impact on insulin sensitivity, adipose differentiation, and cellular autophagy. DESIGN AND PATIENTS: We performed phenotyping studies and molecular screening of PTRF in two unrelated families with CGL. Cellular studies were conducted in cultured skin fibroblasts from the two probands and from control subjects, and in murine 3T3-F442A preadipocytes. Knockdown of cavin-1 or ATG5 was obtained by small interfering RNA-mediated silencing. RESULTS: We identified two new PTRF homozygous mutations (p.Asp59Val or p.Gln157Hisfs*52) in four patients with CGL4 presenting with generalized lipoatrophy and associated metabolic abnormalities. In probands' fibroblasts, cavin-1 expression was undetectable and caveolin-1 and -2 barely expressed. Ultrastructural analysis revealed a loss of membrane caveolae and the presence of numerous cytoplasmic autophagosomes. Patients' cells also showed increased autophagic flux and blunted insulin signaling. These results were reproduced by PTRF knockdown in control fibroblasts and in 3T3-F442A preadipocytes. Cavin-1 deficiency also impaired 3T3-F442A adipocyte differentiation. Suppression of autophagy by small interfering RNA-mediated silencing of ATG5 improved insulin sensitivity and adipocyte differentiation. CONCLUSIONS: This study showed that cavin-1 deficiency resulted in maladaptative autophagy that contributed to insulin resistance and altered adipocyte differentiation. These new pathophysiological mechanisms could open new therapeutic perspectives for adipose tissue diseases including CGL4.


Assuntos
Tecido Adiposo/fisiologia , Autofagia/fisiologia , Caveolina 1/genética , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia Generalizada Congênita/fisiopatologia , Adipogenia/genética , Adolescente , Adulto , Animais , Autofagia/genética , Caveolina 1/deficiência , Diferenciação Celular/genética , Células Cultivadas , Criança , Pré-Escolar , Consanguinidade , Feminino , Fibroblastos/fisiologia , Humanos , Resistência à Insulina/genética , Masculino , Camundongos , Pessoa de Meia-Idade , Adulto Jovem
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