RESUMO
Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine function). It mainly refers to lipodystrophy syndromes with subcutaneous adipose tissue atrophy and/or altered body distribution of adipose tissue leading to insulin resistance, diabetes, hepatic steatosis, dyslipidemia, cardiovascular complications and polycystic ovary syndrome in women. Those syndromes are congenital or acquired, and lipoatrophy is partial or generalized. The diagnosis of lipodystrophy syndromes is often unrecognized, delayed and/or inaccurate, while it is of major importance to adapt investigations to search for specific comorbidities, in particular cardiovascular involvement, and set up multidisciplinary care, and in some cases specific treatment. Physicians have to recognize the clinical and biological elements allowing to establish the diagnosis. Lipodystrophic syndromes should be considered, notably, in patients with diabetes at a young age, with a normal or low BMI, negative pancreatic autoantibodies, presenting clinical signs of lipodystrophy and insulin resistance (acanthosis nigricans, hyperandrogenism, hepatic steatosis, high insulin doses). The association of diabetes and a family history of severe and/or early cardiovascular disease (coronary atherosclerosis, cardiomyopathy with rhythm and/or conduction disorders) may reveal Dunnigan syndrome, the most frequent form of familial lipodystrophy, due to LMNA pathogenic variants. Clinical assessment is primarily done through clinical examination: acanthosis nigricans, abnormal adipose tissue distribution, lipoatrophy, muscular hypertrophy, acromegaloid or Cushingoid features, lipomas, highly visible subcutaneous veins, may be revealing signs. The amount of circulating adipokines may reflect of adipose dysfunction with low leptinemia and adiponectinemia. Other biological metabolic parameters (hypertriglyceridemia, hyperinsulinemia, increased glycemia and hepatic enzymes) may also represent markers of insulin resistance. Quantification of total body fat by impedancemetry or dual-photon X-ray absorptiometry (DEXA) reveals decreased total body mass, in correlation with adipose tissue atrophy; metabolic magnetic resonance imaging can also quantify intraperitoneal and abdominal fat and the degree of hepatic steatosis. Histological analysis of adipose tissue showing structural abnormalities should be reserved for clinical research. Acquired lipodystrophic syndromes most often lead to similar clinical phenotype as congenital syndromes with generalized or partial lipoatrophy. The most frequent causes are old anti-HIV therapy or glucocorticoid treatments. Family history, history of treatments and clinical examination, including a careful physical examination, are keys for diagnosis.
Assuntos
Tecido Adiposo , Lipodistrofia , Humanos , Lipodistrofia/diagnóstico , Tecido Adiposo/patologia , Feminino , Resistência à Insulina/fisiologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/complicaçõesRESUMO
BACKGROUND: Rare syndromes of lipodystrophy and insulin-resistance display heterogeneous clinical expressions. Their early recognition, diagnosis and management are required to avoid long-term complications. OBJECTIVE: We aimed to evaluate the patients' age at referral to our dedicated national reference center in France and their elapsed time from first symptoms to diagnosis and access to specialized care. PATIENTS AND METHODS: We analyzed data from patients with rare lipodystrophy and insulin-resistance syndromes referred to the coordinating PRISIS reference center (Adult Endocrine Department, Saint-Antoine Hospital, AP-HP, Paris), prospectively recorded between 2018 and 2023 in the French National Rare Disease Database (BNDMR, Banque Nationale de Données Maladies Rares). RESULTS: A cohort of 292 patients was analyzed, including 208 women, with the following diagnosis: Familial Partial LipoDystrophy (FPLD, n = 124, including n = 67 FPLD2/Dunnigan Syndrome); Acquired lipodystrophy syndromes (n = 98, with n = 13 Acquired Generalized Lipodystrophy, AGL); Symmetric cervical adenolipomatosis (n = 27, Launois-Bensaude syndrome, LB), Congenital generalized lipodystrophy (n = 18, CGL) and other rare severe insulin-resistance syndromes (n = 25). The median age at referral was 47.6 years [IQR: 31-60], ranging from 25.2 (CGL) to 62.2 years old (LB). The median age at first symptoms of 27.6 years old [IQR: 16.8-42.0]) and the median diagnostic delay of 6.4 years [IQR: 1.3-19.5] varied among diagnostic groups. The gender-specific expression of lipodystrophy is well-illustrated in the FPLD2 group (91% of women), presenting with first signs at 19.3 years [IQR: 14.4-27.8] with a diagnostic delay of 10.5 years [IQR: 1.8-27.0]. CONCLUSION: The national rare disease database provides an important tool for assessment of care pathways in patients with lipodystrophy and rare insulin-resistance syndromes in France. Improving knowledge to reduce diagnostic delay is an important objective of the PRISIS reference center.
Assuntos
Resistência à Insulina , Lipodistrofia , Humanos , Feminino , Masculino , Resistência à Insulina/fisiologia , Lipodistrofia/diagnóstico , Lipodistrofia/metabolismo , Adulto , Pessoa de Meia-Idade , Adulto Jovem , França , Adolescente , Encaminhamento e ConsultaRESUMO
PURPOSE: The differential diagnosis of lipodystrophy involves other disorders characterized by severe fat loss and may be sometimes challenging. Owing to the rarity of lipodystrophy, it is relevant to search for tools and assays that differentiate it from other diseases that may mimic it. We conducted a study on leptin and high molecular weight (HMW) adiponectin serum concentrations in a series of patients diagnosed with lipodystrophy and compared them with those found in anorexia nervosa, one of the illnesses that may be cause of a missed diagnosis of lipodystrophy. METHODS: Leptin and HMW adiponectin serum concentrations were measured in six patients diagnosed with generalized lipodystrophy (GL), six with progeroid syndromes (PS), 13 with familial partial lipodystrophy type 1 (FPLD1, Kobberling syndrome), 10 with familial partial lipodystrophy type 2 (FPLD2, Dunnigan syndrome), 18 with acquired partial lipodystrophy (APL) and 12 affected by anorexia nervosa (AN). Measurements were compared to those obtained in 12 normal weight healthy subjects. RESULTS: Serum leptin concentrations were reduced to a similar degree in GL, PS and AN, proportionally to the extent of fat loss. Serum concentrations of HMW adiponectin were found extremely low in patients with GL and PS, while comparable to normal weight subjects in patients with AN. CONCLUSION: Serum HMW adiponectin can be regarded as a useful tool to discriminate between generalized lipodystrophy syndromes (including PS) and AN.
Assuntos
Adiponectina , Anorexia Nervosa , Leptina , Humanos , Anorexia Nervosa/sangue , Anorexia Nervosa/diagnóstico , Adiponectina/sangue , Feminino , Adulto , Diagnóstico Diferencial , Adolescente , Leptina/sangue , Masculino , Adulto Jovem , Lipodistrofia Generalizada Congênita/sangue , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia/sangue , Lipodistrofia/diagnóstico , Criança , Biomarcadores/sangue , Pessoa de Meia-Idade , Estudos de Casos e ControlesRESUMO
OBJECTIVE: Underdiagnosis is an important issue in genetic lipodystrophies, which are rare diseases with metabolic, cardiovascular, gynecological, and psychological complications. We aimed to characterize the diagnostic pathway in these diseases from the patients' perspective. DESIGN: Cross-sectional study conducted through a self-reported patient questionnaire. METHODS: Patients with genetic lipodystrophy were recruited throughout the French national reference network for rare diseases of insulin secretion and insulin sensitivity. Patients completed a self-reported questionnaire on disease symptoms, steps leading to the diagnosis, and healthcare professionals involved. Descriptive analyses were conducted. RESULTS: Out of 175 eligible patients, 109 patients (84% women) were included; 93 had partial familial lipodystrophy and 16 congenital generalized lipodystrophy. Metabolic comorbidities (diabetes 68%, hypertriglyceridemia 66%, hepatic steatosis 57%), cardiovascular (hypertension 54%), and gynecologic complications (irregular menstruation 60%) were frequently reported. Median age at diagnosis was 30 years (interquartile range [IQR] 23-47). The overall diagnostic process was perceived as "very difficult" for many patients. It extended over 12 years (IQR 5-25) with more than five different physicians consulted by 36% of respondents, before diagnosis, for lipodystrophy-related symptoms. The endocrinologist made the diagnosis for 77% of the patients. Changes in morphotype were reported as the first symptoms by the majority of respondents. CONCLUSIONS: Diagnostic pathway in patients with genetic lipodystrophy is rendered difficult by the multisystemic features of the disease and the lack of knowledge of non-specialized physicians. Training physicians to systematically include adipose tissue examination in routine clinical evaluation should improve diagnosis and management of lipodystrophy and lipodystrophy-associated comorbidities.
Assuntos
Lipodistrofia Generalizada Congênita , Lipodistrofia , Humanos , Feminino , Adulto , Masculino , Estudos Transversais , Doenças Raras , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/genéticaRESUMO
The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.
Assuntos
Lipodistrofia Generalizada Congênita , Lipodistrofia , Adolescente , Humanos , Adulto , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/epidemiologia , Espanha/epidemiologia , Estudos Prospectivos , Lipodistrofia/diagnóstico , Lipodistrofia/epidemiologia , Lipodistrofia/genética , SíndromeRESUMO
BACKGROUND: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome is a rare, hereditary, autoinflammatory disease. However, there are few cases reported in the literature. Therefore, we conduct this systematic review to summarize current evidence. METHODS: We conducted a systematic search in July 2021 using 11 different electronic databases. The included articles were screened according to our inclusion and exclusion criteria and assessed using an appropriate quality assessment tool. Then, the relevant data were extracted and summarized in tables accordingly. Each step of the previous one was done by 3 independent reviewers, and the conflicts were resolved by discussion and sometimes by counseling a senior member. RESULTS: The final included studies were 18 articles with 34 cases (mean age = 8 years, male/female = 19/15). The most reported symptoms and signs were fever 97.1%, erythematous plaques 76.5%, arthralgia 67.6%, hepatomegaly 61.8%, violaceous hue 61.8%, lipodystrophy in extremities 53.1% in addition to low weight and height. Rare features were reported too. The laboratories were not specific, which may be explained by a systemic inflammatory response. Vasculitis was the dominant feature in the skin biopsy, whereas the calcification in the basal ganglia was a prominent sign in many cases. CONCLUSIONS: Fever, skin lesions, and systemic inflammatory response were the prominent features of chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome. The clinical picture is the main guide in addition to the pathological findings. Mutation detection is the confirmatory test. Prednisolone is the most effective reported treatment for acute presentations in the literature.
Assuntos
Dermatite , Lipodistrofia , Dermatopatias , Síndrome de Sweet , Humanos , Masculino , Feminino , Criança , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamento farmacológico , Síndrome de Sweet/patologia , Dermatopatias/diagnóstico , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia/patologia , Febre/diagnóstico , Doença Crônica , Síndrome de Resposta Inflamatória SistêmicaRESUMO
Until recently, mandibuloacral dysplasia (MAD) with type A and type B lipodystrophy was the first to come to mind in the association of mandibular hypoplasia, lipodystrophy, and acro-osteolysis. However, it has recently been added to the differential diagnosis of MAD, a newly defined syndrome, called MDPS. MDPS is a skeletal dysplasia characterized by postnatal growth retardation, hypotonia, generalized lipodystrophy, skin changes, progeroid traits, and dysmorphic facial features, including prominent eyes, long pinched nose, mandibular hypoplasia, and a small mouth. Biallelic null variants of the MTX2 gene are responsible for this syndrome. We performed whole-exome sequencing (WES) in a 6-year-old patient with skeletal dysplasia. WES revealed a novel homozygous c.543+1G>T splice site variant in the MTX2 gene. We also extracted total RNA from peripheral blood and used reverse transcription-polymerase chain reaction to generate cDNA. Sanger sequencing from cDNA showed that exon 8 of MTX2 was skipped. This study adds to the genetics and phenotype of MDPS and underlines the importance of comprehensive clinical and molecular research.
Assuntos
Acro-Osteólise , Lipodistrofia , Micrognatismo , Humanos , Mutação , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Acro-Osteólise/genética , Homozigoto , Éxons/genética , Micrognatismo/genética , SíndromeRESUMO
RESUMEN La obesidad y el sobrepeso se definen como una acumulación anormal o excesiva de grasa que puede ser perjudicial para la salud. Es una enfermedad crónica de origen multifactorial, que como consecuencia ocasiona problemas higiénicos, discapacidad funcional y alteración de la calidad de vida. La dermolipectomía abdominal es una técnica quirúrgica que constituye la única opción para el tratamiento de pacientes con panículo adiposo prominente; de esa forma se logra disminuir las complicaciones y se reintegra socialmente al paciente que, a causa del enorme faldón abdominal, estuvo limitado por muchos años. Presentamos el caso de una paciente de 53 años con lipodistrofia abdominal grave, que llegaba a ambos tobillos con afectación cutánea, y discapacidad para realizar actividades diarias, resuelta con dermolipectomía abdominal y resección de 29 kg de tejido dermograso. Se realizará, además, una revisión bibliográfica del tema.
ABSTRACT Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. It is a chronic disease caused by multiple factors, which results in hygienic issues, functional disability and impaired quality of life. Abdominal dermolipectomy is the only surgical option for the treatment of patients with prominent panniculus morbidus, thus reducing complications and providing social reintegration for the patient who has been limited for many years due to the enormous abdominal panniculus. We report the case of a 53-year-old female patient with severe abdominal lipodystrophy with coverage of both ankles, skin involvement, and disability to perform daily activities, that was managed with abdominal dermolipectomy and resection of 29 kg of dermo-adipose tissue. Bibliographic research is also presented.
Assuntos
Feminino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Lipodistrofia/cirurgia , Obesidade Mórbida/complicações , Parede Abdominal/cirurgia , Infecções , Lipodistrofia/diagnósticoRESUMO
PURPOSE OF REVIEW: Genetic or acquired lipodystrophies are characterized by selective loss of body fat along with predisposition towards metabolic complications of insulin resistance, such as diabetes mellitus, hypertriglyceridemia, hepatic steatosis, polycystic ovarian syndrome, and acanthosis nigricans. In this review, we discuss the various subtypes and when to suspect and how to diagnose lipodystrophy. RECENT FINDINGS: The four major subtypes are autosomal recessive, congenital generalized lipodystrophy (CGL); acquired generalized lipodystrophy (AGL), mostly an autoimmune disorder; autosomal dominant or recessive familial partial lipodystrophy (FPLD); and acquired partial lipodystrophy (APL), an autoimmune disorder. Diagnosis of lipodystrophy is mainly based upon physical examination findings of loss of body fat and can be supported by body composition analysis by skinfold measurements, dual-energy x-ray absorptiometry, and whole-body magnetic resonance imaging. Confirmatory genetic testing is helpful in the proband and at-risk family members with suspected genetic lipodystrophies. The treatment is directed towards the specific comorbidities and metabolic complications, and there is no treatment to reverse body fat loss. Metreleptin should be considered as the first-line therapy for metabolic complications in patients with generalized lipodystrophy and for prevention of comorbidities in children. Metformin and insulin therapy are the best options for treating hyperglycemia and fibrates and/or fish oil for hypertriglyceridemia. Lipodystrophy should be suspected in lean and muscular subjects presenting with diabetes mellitus, hypertriglyceridemia, non-alcoholic fatty liver disease, polycystic ovarian syndrome, or amenorrhea. Diabetologists should be aware of lipodystrophies and consider genetic varieties as an important subtype of monogenic diabetes.
Assuntos
Diabetes Mellitus , Hipertrigliceridemia , Lipodistrofia Generalizada Congênita , Lipodistrofia , Síndrome do Ovário Policístico , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Feminino , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia Generalizada Congênita/complicações , Imageamento por Ressonância Magnética/efeitos adversos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/genética , Imagem Corporal Total/efeitos adversosRESUMO
Leptin replacement therapy (LRT) has drastically improved the prognosis of patients with lipodystrophy, but pro-inflammatory properties of leptin could become evident in the long term. Here, we report a 30-year-old Japanese woman with generalized lipodystrophy-associated progeroid syndrome due to a heterozygous LMNA variant (c.29C > T; p.T10I), who was diagnosed with severe aortic stenosis (AS) after more than a decade of LRT, which required transcatheter aortic valve implantation. Given her marked hypoadiponectinemia and the LMNA variant, our patient might have been susceptible to progeria-associated disorders, including aortic stenosis, which could have been exaggerated by the prolonged 'imbalanced adipokines' caused by LRT between pro-inflammatory leptin and anti-inflammatory adiponectin. Thus, long-term LRT could be associated with AS in patients with the LMNA variant to cause generalized lipodystrophy-associated progeroid syndrome and hypoadiponectinemia.
Assuntos
Estenose da Valva Aórtica , Lipodistrofia Generalizada Congênita , Lipodistrofia , Adiponectina/deficiência , Adulto , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Feminino , Humanos , Lamina Tipo A/genética , Leptina , Lipodistrofia/complicações , Lipodistrofia/diagnóstico , Lipodistrofia Generalizada Congênita/complicações , Erros Inatos do MetabolismoRESUMO
Generalized lipodystrophy (GL) syndromes are a group of rare heterogenous disorders, characterized by total subcutaneous fat loss. The frequency of GL is currently assessed as approximately 0,23 cases per million of the population, in Europe - as 0,96 cases per million of the population. They can be congenital (CGL) or acquired (AGL) depending on the etiology and the time of the onset of fat loss. Both CGL and AGL are often associated with different metabolic complications, such as hypertriglyceridemia, insulin resistance and lipoatrophic diabetes mellitus, metabolically associated FLD, arterial hypertension, proteinuria, reproductive system disorders. In this review we aimed to summarize the information on all forms of generalized lipodystrophy, especially the ones of genetic etiology, their clinical manifestations and complications, the perspectives for diagnostics, treatment and further research.
Assuntos
Lipodistrofia , Aciltransferases/genética , Idade de Início , Caveolina 1/genética , Proteínas de Ligação a DNA/genética , Diabetes Mellitus Lipoatrófica/complicações , Diagnóstico Diferencial , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Doenças Genitais/complicações , Humanos , Hipertensão/complicações , Hipertrigliceridemia/complicações , Resistência à Insulina , Lamina Tipo A/genética , Lipodistrofia/classificação , Lipodistrofia/diagnóstico , Lipodistrofia/etiologia , Lipodistrofia/genética , Lipodistrofia Generalizada Congênita/classificação , Lipodistrofia Generalizada Congênita/genética , Mandíbula/anormalidades , Proteínas de Membrana/genética , Metaloendopeptidases/genética , Mutação , Progéria/genética , Proteinúria/complicações , RNA Polimerase III/genética , Proteínas de Ligação a RNA/genética , Síndrome , Helicase da Síndrome de Werner/genéticaRESUMO
Lipodystrophic syndromes (LS) constitute a clinically and genetically heterogeneous group of diseases characterized by a loss of adipose tissue. These syndromes are usually associated with metabolic complications, which are determinant for morbidity and mortality. The classical forms of LS include partial, generalized, and progeroid lipodystrophies. They are usually due to defects in proteins playing a key role in adipogenesis and adipocyte functions. More recently, systemic disorders combining lipodystrophy and multiple organ dysfunction have been described, including autoinflammatory syndromes, mitochondrial disorders, as well as other complex entities. To date, more than thirty genes have been implicated in the monogenic forms of LS, but the majority of them remain genetically-unexplained. The associated pathophysiological mechanisms also remain to be clarified in many instances. Next generation sequencing-based approaches allow simultaneous testing of multiple genes and have become crucial to speed up the identification of new disease-causing genes. The challenge for geneticists is now the interpretation of the amount of available genetic data, generated especially by exome and whole-genome sequencing. International recommendations on the interpretation and classification of variants have been set up and are regularly reassessed. Very close collaboration between geneticists, clinicians, and researchers will be necessary to make rapid progress in understanding the molecular and cellular basis of these diseases, and to promote personalized medicine.
Assuntos
Lipodistrofia/genética , Aciltransferases/genética , Adipócitos/fisiologia , Adipogenia , GTP Fosfo-Hidrolases/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Inflamação/complicações , Inflamação/genética , Lamina Tipo A/genética , Lipodistrofia/classificação , Lipodistrofia/diagnóstico , Lipomatose Simétrica Múltipla/genética , Doenças Mitocondriais/complicações , Proteínas Mitocondriais/genética , PPAR gama/genética , Complexo de Endopeptidases do Proteassoma/genética , SíndromeRESUMO
OBJECTIVE: Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). METHODS: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. RESULTS: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. CONCLUSION: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.
Assuntos
Subunidades gama da Proteína de Ligação ao GTP , Lipodistrofia Generalizada Congênita , Lipodistrofia , Alelos , Subunidades gama da Proteína de Ligação ao GTP/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/genética , Mutação/genéticaRESUMO
ABSTRACT Objective: Our aim is to establish genetic diagnosis of congenital generalized lipodystrophy (CGL) using targeted massively parallel sequencing (MPS), also known as next-generation sequencing (NGS). Subjects and methods: Nine unrelated individuals with a clinical diagnosis of CGL were recruited. We used a customized panel to capture genes related to genetic lipodystrophies. DNA libraries were generated, sequenced using the Illumina MiSeq, and bioinformatics analysis was performed. Results: An accurate genetic diagnosis was stated for all nine patients. Four had pathogenic variants in AGPAT2 and three in BSCL2. Three large homozygous deletions in AGPAT2 were identified by copy-number variant analysis. Conclusions: Although we have found allelic variants in only 2 genes related to CGL, the panel was able to identify different variants including deletions that would have been missed by Sanger sequencing. We believe that MPS is a valuable tool for the genetic diagnosis of multi-genes related diseases, including CGL.
Assuntos
Humanos , Subunidades gama da Proteína de Ligação ao GTP/genética , Lipodistrofia Generalizada Congênita/diagnóstico , Lipodistrofia Generalizada Congênita/genética , Lipodistrofia/diagnóstico , Lipodistrofia/genética , Alelos , Sequenciamento de Nucleotídeos em Larga Escala , Mutação/genéticaAssuntos
Lipodistrofia/induzido quimicamente , Fígado/diagnóstico por imagem , Nivolumabe/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Antineoplásicos Imunológicos/efeitos adversos , Biópsia , Feminino , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/imunologia , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/imunologia , Neoplasias Cutâneas/tratamento farmacológicoAssuntos
Reação no Local da Injeção/etiologia , Lipodistrofia/etiologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Lactente , Reação no Local da Injeção/diagnóstico , Reação no Local da Injeção/patologia , Reação no Local da Injeção/terapia , Injeções Intramusculares/efeitos adversos , Injeções Subcutâneas , Lipodistrofia/diagnóstico , Lipodistrofia/patologia , Lipodistrofia/terapia , Masculino , Estudos Retrospectivos , Gordura Subcutânea/patologia , Gordura Subcutânea/transplante , Tacrolimo/administração & dosagem , Transplante Autólogo , Resultado do TratamentoRESUMO
PURPOSE: Lipodystrophy is a collection of rare disorders defined by complete or partial loss of adipose tissue, due to abnormal adipocyte production, function, or distribution; it shares the main metabolic complications with obesity. Aims of the present study were to investigate the psychopathological characteristics of non-HIV lipodystrophic patients in comparison with a group of obese patients, a group of patients affected by oncologic chronic illness, and a control group of healthy subjects. METHODS: All participants were female: 16 non-HIV lipodystrophic women (mean age 42 ± 12 years), 20 women with breast cancer (adenocarcinoma with a positive sentinel lymph node in outpatients awaiting chemotherapy, mean age 44 ± 5 years), 20 obese women (mean age 40 ± 3 years), and 20 healthy women (mean age 40 ± 2 years). Each lipodystrophic patient received a psychiatric assessment, following the diagnostic criteria for DSM-5. Patients and controls received a battery of self-report instruments measuring general psychopathology, body image concerns, eating habits and food craving, and pain concerns. The following psychopathological rating scales were used: SCL-90-R (Symptom Check List) for general psychopathology, BUT (Body Uneasiness Test) for body image, FCQ-T (Food Cravings Questionnaire Trait) for food craving, and WHYMPI (West Haven Yale Multidimensional Pain Inventory) for multidimensional pain inventory. RESULTS: The psychiatric assessment of the 16 lipodystrophic patients revealed: three lifetime mood disorder, six current mood disorder, six lifetime anxiety disorder, five current anxiety disorder, four current somatic symptom disorder with predominant pain, six current binge eating disorder, 11 eating disorder not otherwise specified, two borderline personality disorder, one obsessive-compulsive personality disorder, one avoidant personality disorder, and five personality disorder not otherwise specified. In SCL-90-R scale, the subscale sensitivity showed a significantly higher score in the lipodystrophic and oncologic groups compared to healthy subjects. The subscale paranoid ideation showed a significantly higher score in the lipodystrophic group vs all the other groups. The total score of BUT scale was significantly higher in the lipodystrophic compared to healthy subjects. In WHYMPI scale, the scores of pain interference and family support were significantly higher in the lipodystrophic group. The scores of negative responses were significantly higher in the lipodystrophic group vs healthy subjects. In FCQ-T scale, the score of Cues dimension in lipodystrophic patients was significantly lower as compared with all the other groups. CONCLUSIONS: Our findings suggest that lipodystrophic patients have an increased prevalence of mood, anxiety, pain, and eating disorders. LEVEL OF EVIDENCE: Level III. Evidence obtained from case-control analytic study.
Assuntos
Transtorno da Compulsão Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Lipodistrofia , Adulto , Transtornos de Ansiedade , Feminino , Humanos , Lipodistrofia/complicações , Lipodistrofia/diagnóstico , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade , Escalas de Graduação PsiquiátricaRESUMO
Translation is the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public, ranging from diagnostics and therapeutics to medical procedures and behavioral changes. Translational research is defined as the effort to traverse a particular step of the translation process for a particular target or disease. Translational science is a newly emerging science, distinct from basic and clinical sciences in biology and medicine, and is a field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Advances in translational science will increase the efficacy and safety of translational research in all diagnostic and therapeutic areas. This report examines translational research on novel hormones, the natriuretic peptide family and leptin, which have achieved clinical applications or for which studies are still ongoing, and also emphasizes the lessons that translational science has learned from more than 30 years' experience in translational research.
Assuntos
Leptina/metabolismo , Leptina/farmacologia , Peptídeos Natriuréticos/metabolismo , Peptídeos Natriuréticos/farmacologia , Pesquisa Translacional Biomédica , Acondroplasia/diagnóstico , Acondroplasia/terapia , Animais , Humanos , Lipodistrofia/diagnóstico , Lipodistrofia/terapia , Doenças Raras/diagnóstico , Doenças Raras/terapiaRESUMO
Lipodystrophies are a heterogeneous group of syndromes defined by a severe reduction of the adipose tissue. These can be congenital or acquired. Anatomically, they can be partial or generalized. The etiology of several lipodystrophies is well known. However, the cause of many others remains unknown. The commonest lipodystrophy worldwide is secondary to highly active anti-retroviral therapy in HIV-infected patients. By contrast, primary lipodystrophies (those not associated to any known disease or condition) are much less common and represent a diagnostic challenge. The major complications of lipodystrophies are metabolic, often resulting in severe insulin resistance, diabetes and dyslipidemia. No cure is available for lipodystrophies but the supplementation with recombinant leptin potently controls the metabolic abnormalities when there is a leptin deficiency. Herein, we review the clinical presentation, diagnostic process and therapeutic principles of the main primary lipodystrophy syndromes.