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BACKGROUND: The incapacity to store lipids in adipose tissue in Congenital Generalized Lipodystrophy (CGL) causes hypoleptinemia, increased appetite, ectopic fat deposition and lipotoxicity. CGL patients experience shortened life expectancy. The plasma lipidomic profile has not been characterized fully in CGL, nor has the extent of dietary intake in its modulation. The present work investigated the plasma lipidomic profile of CGL patients in comparison to eutrophic individuals at the fasted state and after a breakfast meal. METHOD: Blood samples from 11 CGL patients and 10 eutrophic controls were collected after 12 h fasting (T0) and 90 min after an ad libitum fat-containing breakfast (T90). The lipidomic profile of extracted plasma lipids was characterized by non-target liquid chromatography mass spectrometry. RESULTS: Important differences between groups were observed at T0 and at T90. Several molecular species of fatty acyls, glycerolipids, sphingolipids and glycerophospholipids were altered in CGL. All the detected fatty acyl molecular species, several diacylglycerols and one triacylglycerol species were upregulated in CGL. Among sphingolipids, one sphingomyelin and one glycosphingolipid species showed downregulation in CGL. Alterations in the glycerophospholipids glycerophosphoethanolamines, glycerophosphoserines and cardiolipins were more complex. Interestingly, when comparing T90 versus T0, the lipidomic profile in CGL did not change as intensely as it did for control participants. CONCLUSIONS: The present study found profound alterations in the plasma lipidomic profile of complex lipids in CGL patients as compared to control subjects. A fat-containing breakfast meal did not appear to significantly influence the CGL profile observed in the fasted state. Our study may have implications for clinical practice, also aiding to a deeper comprehension of the role of complex lipids in CGL in view of novel therapeutic strategies.

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Cystic bone lesions are the hallmark of skeletal abnormalities in patients with congenital generalized lipodystrophy (CGL). However, their pathophysiology is still unclear and theories about their origin remain largely speculative. This article reports on a patient with CGL and cystic bone lesions, some of them with unusual magnetic resonance imaging (MRI) findings that include elevated signal intensity on T1-weighted images and fluid-fluid levels, the latter evolving to a more "classic" cystic appearance on follow-up. Even though similar findings were first described almost 30 years ago, little attention was given to them back then; furthermore, other than the present report, no other study has performed sequential exams to follow their evolution in serial MRI. The authors conduct a review of the literature, hypothesizing that these remarkable findings may reflect an intermediate stage in the process of cystification of the abnormal bone marrow, incapable to perform adipose conversion, lending factual support to the modern theories about this issue.

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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)

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Congenital Generalized Lipodystrophy (CGL) is a rare syndrome characterized by the almost total absence of subcutaneous adipose tissue due to the inability of storing lipid in adipocytes. Patients present generalized lack of subcutaneous fat and normal to low weight. They evolve with severe metabolic disorders, non-alcoholic fatty liver disease, early cardiac abnormalities, and infectious complications. Although low body weight is a known risk factor for osteoporosis, it has been reported that type 1 and 2 CGL have a tendency of high bone mineral density (BMD). In this review, we discuss the role of bone marrow tissue, adipokines, and insulin resistance in the setting of the normal to high BMD of CGL patients. Data bases from Pubmed and LILACS were searched, and 113 articles published until 10 April 2021 were obtained. Of these, 76 were excluded for not covering the review topic. A manual search for additional literature was performed using the bibliographies of the studies located. The elucidation of the mechanisms responsible for the increase in BMD in this unique model of insulin resistance may contribute to the understanding of the interrelationships between bone, muscle, and adipose tissue in a pathophysiological and therapeutic perspective.

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Paget's disease of bone (PDB) is a common skeleton disorder in which the diagnosis is suggested by radiological analyses. Congenital generalized lipodystrophy (CGL) is a rare, but a radiologic differential diagnosis of Paget's disease. Patients present total or almost total lack of subcutaneous adipose tissue, leptin deficiency, and precocious ectopic lipid accumulation, which lead to intense insulin resistance, poorly controlled diabetes mellitus, and hypertriglyceridemia. CGL subtypes 1 and 2 present sclerosis and osteolytic lesions that can resemble "pagetic" lesions. The clinical correlation is, therefore, essential. We report a CGL patient with bone lesions in which the radiographic findings led to a misdiagnosis of PDB. This case report brings awareness to CGL, a life-threating condition. Its early recognition is essential to avoid clinical complications and premature death. Therefore, it is important to consider CGL as PDB's differential diagnosis, especially in countries with high prevalence of this rare disease, such as Brazil.

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BACKGROUND: A new strain of human coronavirus (HCoV) spread rapidly around the world. Diabetes and obesity are associated with a worse prognosis in these patients. Congenital Generalized Lipodystrophy (CGL) patients generally have poorly controlled diabetes and require extremely high doses of insulin. There is no documentation in the literature of cases of COVID in CGL patients. Thus, we aimed to evaluate the prevalence of SARS-CoV-2 infection in CGL patients, and the association of their clinical and metabolic characteristics and outcomes. METHODS: This is a cross-sectional study carried out between July and October 2020. Clinical data collected were respiratory or other flu-like symptoms, need of hospitalization in the last three months, CGL comorbidities, and medications in use. Cholesterol, triglycerides, glycohemoglobin A1c levels, anti-SARS-CoV-2 antibodies and nasopharyngeal swab for RT-qPCR were also obtained in all CGL patients. Mann-Whitney U test was used to analyze the characteristics of the participants, verifying the non-adherence of the data to the Gaussian distribution. In investigating the association between categorical variables, we used Pearson's chi-square test and Fisher's exact test. A significance level of 5% was adopted. RESULTS: Twenty-two CGL patients were assessed. Eight subjects (36.4%) had reactive anti-SARS-CoV-2 antibodies. Only one of these, also presented detectable RT-qPCR. Five individuals (62.5%) were women, median age of 13.5 years (1 to 37). Symptoms like fever, malaise, nausea, diarrhea and chest pain were present, and all asymptomatic patients were children. All subjects had inadequate metabolic control, with no difference between groups. Among positive individuals there was no difference between those with AGPAT2 (75%) and BSCL2 gene mutations (25%) (p > 0.05). No patient needed hospitalization or died. CONCLUSIONS: We described a high prevalence of SARS-CoV-2 infection in CGL patients with a good outcome in all of them. These findings suggest that at least young CGL patients infected by SARS-COV-2 are not at higher risk of poor outcome, despite known severe metabolic comorbidities.

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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.

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Resumen Introducción. La lipodistrofia congénita generalizada (LCG) es un síndrome genético autosómico recesivo extremadamente raro que se caracteriza por ausencia generalizada de tejido adiposo, deficiencia en la producción de hormonas como la leptina y complicaciones metabólicas potencialmente serias como diabetes mellitus tipo 2 (DM2), esteatohepatitis e hipertrigliceridemia. Presentación del caso. Paciente femenina de 17 años con un diagnóstico tardío de LCG y con diabetes mellitus (erróneamente clasificada como tipo I), hipertrigliceridemia severa e infecciones a repetición. Luego de introducir metformina y un inhibidor del SGLT2 en el manejo de la paciente, se logró un adecuado control metabólico. Conclusión. Con frecuencia, el desconocimiento de algunas enfermedades huérfanas lleva a diagnósticos erróneos y, por tanto, a tratamientos inadecuados que en algunos casos pueden empeorar la condición clínica de los pacientes. Por lo anterior, en el caso de la LCG, es necesario que la comunidad médica tenga una mejor comprensión de sus aspectos diagnósticos y terapéuticos para brindar un diagnóstico y tratamiento oportunos.

Abstract Introduction: Generalized congenital lipodystrophy (GDL) is an extremely rare autosomal recessive genetic syndrome characterized by generalized absence of adipose tissue, deficient production of hormones such as leptin, and potentially serious metabolic complications such as type 2 diabetes mellitus (DM2), steatohepatitis and hypertriglyceridemia. Case presentation: This is the case of a 17-year-old female patient with a late diagnosis of GDL and with diabetes mellitus (erroneously classified as type 1), severe hypertriglyceridemia and recurrent infections. Adequate metabolic control was achieved after the introduction of metformin and an SGLT2 inhibitor. Conclusion: Lack of knowledge about some orphan diseases usually leads to misdiagnosis and, therefore, to inadequate treatments that may worsen the clinical condition of patients. Therefore, in the case of GDL, the medical community should have a better understanding of its diagnostic and therapeutic aspects in order to provide timely diagnosis and treatment.

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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.

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Congenital generalized lipodystrophy (CGL) is an autosomal recessive rare disease, with a worldwide prevalence of around 1 in every 12 million people. There are several case reports of patients with CGL in Piura, a region in northern Peru; however its regional prevalence is unknown. The objective was to determine the prevalence of CGL in the region of Piura, Peru during the years 2000-2017. A descriptive, observational study was carried out. A search of clinical histories of patients with the diagnosis of CGL attended between 2000 and 2017 in the pediatric and endocrinology services of the reference hospitals of the department of Piura and in the genetic and endocrinology services of the "Instituto Nacional de Salud del Niño". A patient was considered to have CGL if they met the clinical criteria and or if they had a molecular diagnosis, in addition to patients with CGL from the department of Piura reported in previous publications. A total of 23 cases of CGL were found in Piura, the highest prevalence was in 2014 with 1.2 per 100,000 people, and by 2017 the prevalence was 0.86 per 100,000 people. In conclusion, the department of Piura has a high prevalence of CGL.

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Background: Dunnigan-type familial partial lipodystrophy (FPLD2) is a rare autosomal dominant disease caused by heterozygous mutations in the LMNA gene that results in regional loss of subcutaneous adipose tissue with onset in puberty. However, a generalized lipodystrophy phenotype has also been associated with heterozygous mutations in this gene, demonstrating the noticeable phenotypic heterogeneity of this disease. Methods: We report and describe clinical and metabolic features of four patients from the same family with the p.R582C LMNA mutation, three homozygous and one in the heterozygous state that present with three distinct lipodystrophic phenotypes. Results: Case description: The proband was a 12-year-old girl who developed severe subcutaneous fat atrophy in limbs and abdomen followed by a remarkable dorsocervical fat accumulation in adulthood along with diabetes at age 23. The proband's sister was a phenotypically normal girl who developed hypertriglyceridemia at age 8, progressive features of partial lipodystrophy at age 11, and diabetes at age 22. The proband's mother was first examined at age 32, presenting diabetes and a severe generalized lipodystrophic phenotype; she developed kidney failure at age 41 and died due to diabetic complications. The proband's father was a 50-year-old man with abdominal fat concentration that was initially considered phenotypically normal. Massively parallel sequencing using a platform of genes related to genetic lipodystrophies, followed by Sanger sequencing, revealed the transversion c.1744C>T at exon 11 of the LMNA gene (p.R582C) in the homozygous (mother and daughters) and heterozygous (father) states. Conclusion: We documented three distinct phenotypes of the homozygous and heterozygous p. R582C LMNA mutation in the same kindred, illustrating that FPLD2 linked to mutations in this gene is a disease of great clinical heterogeneity, possibly due to associated environmental or genetic factors.

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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.

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BACKGROUND: Congenital generalized lipodystrophy (CGL) produces clinical features with severe metabolic consequences. Research has focused on measuring the response to the drugs. Nevertheless, there are no studies on the response to dietary therapy. The aim of this study was to show the clinical response to early nutritional intervention to modify or reverse metabolic effects in pediatric patients with CGL. METHODS: A retrospective study was conducted on patients with CGL followed up between January 2003 and June 2017. After diagnosis, patients were indicated a diet with a total calorie intake according to the reference daily intake (RDI), without fast sugars. Clinical feature and laboratory tests (insulin, glucose, A1C, lipid panel, liver and kidney function tests), and complementary studies (abdominal ultrasonography, echocardiogram), at the first visit and during follow-up were recorded. Statistics, version 10, was used for analysis. RESULTS: Eight patients were included. The median age at the first visit was 1.1 years (range, 0.28-9.9 years) and the median time of follow-up was 3.9 years (range, 0.4-9.47 years). The median initial triglyceride level was 516 mg/dL (range, 327-3590 mg/dL) p=0.014; median low-density lipoprotein (LDL) was 157 mg/dL (range, 94-370 mg/dL) p=0.03; median glycemia was 84 mg/dL (range, 63-126 mg/dL) p=0.02; median insulin was 28.84 µUI/mL (range, 3.9-116); median homeostatic model assessment-insulin resistance (HOMA-IR) was 5.3 (range, 1.21-23.2). After 3-6 months of diet, the median percentage of triglyceride decrease was 79.5% (range, 47-97%), LDL 44% (range, 20.5-59%), glycemia 8.8% (range, 0-53.1%), insulin 67.8% (range, 0-92.8%) p=0.02 and HOMA-IR was 81.5% (range, 50-98%) p=0.05. As of the last follow-up visit, in none of the patients, liver ultrasonography or echocardiogram had deteriorated. CONCLUSIONS: In these pediatric patients with CGL, a diet adjusted to RDI with restriction of fast sugars led to a marked improvement in metabolic parameters.

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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)

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Congenital generalized lipodystrophy (CGL) is a genetically heterogeneous group of disorders characterized by the absence of functional adipose tissue. We identified two pedigrees with CGL in the community of the Mestizo tribe in the northern region of Peru. Five cases, ranging from 15 months to 7 years of age, presented with generalized lipodystrophy, muscular prominence, mild intellectual disability, and a striking aged appearance. Sequencing of the BSCL2 gene, known to be mutated in type 2 CGL (CGL2; Berardinelli-Seip syndrome), revealed a homozygous deletion of exon 3 in all five patients examined, suggesting the presence of a founder mutation. This intragenic deletion appeared to be mediated by recombination between Alu sequences in introns 2 and 3. CGL2 in this population is likely underdiagnosed and undertreated because of its geographical, socio-economic, and cultural isolation.© 2016 Wiley Periodicals, Inc.

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Generalized lipodystrophy (GL) is a rare inherited or acquired disease characterized by widespread loss of subcutaneous fat, leading to leptin deficiency, ectopic fat deposition, and severe metabolic abnormalities. Previous studies have shown the benefit of leptin replacement (metreleptin) in ameliorating metabolic complications, but little is known about the experience of metreleptin treatment outside of a research setting. We report on post-marketing clinical experience with metreleptin therapy in three patients with GL and marked hypoleptinemia, uncontrolled diabetes, and hypertriglyceridemia. After metreleptin treatment for 12-168 weeks, the mean glycated hemoglobin decreased from 10.9% to 5.8%, and serum triglycerides were normalized (a mean decline of 90%). These benefits were observed within weeks of starting therapy, were durable, and were accompanied by subjective improvements in quality of life, decreased need for concomitant medications, and no significant adverse effects. Metreleptin was safe and effective in normalizing certain severe metabolic abnormalities in the clinic setting.

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La asociación entre la lipodistrofia congénita generalizada y la anomalía de Dandy Walker no es habitual. Se reporta el caso de una niña de 1 año de edad que ingresa al hospital a los 4 meses por riesgo social, con diagnóstico de anomalía de Dandy Walker. Durante su internación, se evidencia en forma progresiva aspecto acromegaloide, facies triangular, hirsutismo, lipoatrofia, hipertrofia muscular, clitoromegalia, distensión abdominal con hepatomegalia progresiva e hpertrigliceridernia. Se arriba así al diagnóstico clínico de lipodistrofia congénita generalizada. Se revisan los aspectos clínicos y el seguimiento interdisciplinario para la detección oportuna de insulinorresistencia y diabetes, pubertad precoz, miocardiopatía, entre otras. Respecto de la anomalía de Dandy Walker, se realizan controles evolutivos en búsqueda de la aparición de signos de hipertensión endocraneana. Por el carácter autosómico recesivo de la lipodistrofia congénita generalizada, es importante realizar el asesoramiento genético a los padres.

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance shouldbe given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.

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La asociación entre la lipodistrofia congénita generalizada y la anomalía de Dandy Walker no es habitual. Se reporta el caso de una niña de 1 año de edad que ingresa al hospital a los 4 meses por riesgo social, con diagnóstico de anomalía de Dandy Walker. Durante su internación, se evidencia en forma progresiva aspecto acromegaloide, facies triangular, hirsutismo, lipoatrofia, hipertrofia muscular, clitoromegalia, distensión abdominal con hepatomegalia progresiva e hpertrigliceridernia. Se arriba así al diagnóstico clínico de lipodistrofia congénita generalizada. Se revisan los aspectos clínicos y el seguimiento interdisciplinario para la detección oportuna de insulinorresistencia y diabetes, pubertad precoz, miocardiopatía, entre otras. Respecto de la anomalía de Dandy Walker, se realizan controles evolutivos en búsqueda de la aparición de signos de hipertensión endocraneana. Por el carácter autosómico recesivo de la lipodistrofia congénita generalizada, es importante realizar el asesoramiento genético a los padres.(AU)

The objective of this study is to describe the unexpected association between the congenital generalized lipodystrophy (CGL) and Dandy Walker anomaly. We report the case of a 1-year-old infant who was hospitalized at her fourth month of life with Dandy Walker anomaly diagnosis and an increased social risk. During her hospitalization, she developed progressively: acromegaloid aspect, triangular fascia, hirsutism, lipoatrophy, muscle hypertrophy, clitoromegaly, abdominal distention, progressive hepatomegaly, and hypertriglyceridemia. This led to the clinical diagnosis of congenital generalized lipodystrophy. Importance shouldbe given to the examination of clinical aspects as well as the interdisciplinary follow-up for proper detection of insulin resistance and diabetes, early puberty, cardiomyopathy, among others. In case of Dandy Walker anomaly, it should be checked the evolution to search intracranial hypertension signs. Due to its autosomal recessive nature, it is important to provide genetic counseling to the parents.(AU)

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Resumen: El síndrome de Berardinelli-Seip, una lipodistrofia congénita, es una enfermedad metabólicarara que se caracteriza por una lipodistrofia generalizada grave, resistencia a la insulinay dislipidemia. La enfermedad se asocia con varias manifestaciones dermatológicas y sistémicas.Las complicaciones incluyen miocardiopatía hipertrófica, hígado graso con disfunción hepática,hipertrofia muscular y varias alteraciones endocrinas. Se presenta un caso de este tipode lipodistrofia en una mujer de 18 años de edad, que ingresa con un cuadro de hiperglucemia sinevidencia de cetoacidosis o de estado hiperosmolar hiperglucémico, con hepatomegalia, signosde resistencia a la insulina y ausencia de tejido adiposo. Después de los análisis complementarios,se le diagnosticó síndrome de Berardinelli-Seip. El reconocimiento temprano de la lipodistrofiacongénita es esencial para prevenir las complicaciones, y permite una asesoría genética y reproductivade los pacientes y sus familias. Se incluye también una breve revisión de la literatura.

Abstract: Berardinelli-Seip congenital lipodystrophy is a rare metabolic disorder characterized bysevere generalized lipodystrophy, insulin resistance, and dyslipedemia. The condition is associatedwith various dermatological and systemic manifestations. Complications include hypertrophiccardiomyopathy, a fatty liver with hepatic dysfunction, muscular hypetrophy, and various endocrinedisturbances. We report a case of this form of lipodystrophy in an 18-year-old female who wasadmitted with hyperglycaemia without evidence of ketoacidosis or hyperglycemic hyperosmolarstate, with hepatomegaly, signs of insulin resistance and absence of adipose tissue. After furtherinvestigation, a diagnosis of Berardinelli-Seip syndrome was made. Early recognition of congenitallipodystrophy is essential to prevent complications, and allows genetic and reproductive counselingto patients and their families. A brief review of the literature is also included.

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OBJETIVO: Descrever o perfil genético e metabólico de portadores da síndrome de Berardinelli-Seip (BSCL) acompanhados no Instituto da Criança do HC-FMUSP. SUJEITOS E MÉTODOS: Pacientes com as características clínicas da BSCL (n = 5), todas do sexo feminino, foram avaliadas com dosagens de glicose e insulina, lípides, leptina, enzimas hepáticas, análise de DNA, ultrassonografia abdominal. RESULTADOS: A deficiência de leptina e a hipertrigliceridemia foram constatadas nas cinco pacientes. Três evoluíram para diabetes melito (DM). Quatro tiveram mutação no gene AGPAT2 e uma no gene CAV1. CONCLUSÃO: As alterações metabólicas mais precoces foram a hipertrigliceridemia e a resistência insulínica, culminando no surgimento do DM à época da puberdade, sendo as mutações no gene AGPAT2 as mais frequentes em nossa casuística.

OBJECTIVE: To report the genetic and metabolic profile of patients with Berardinelli-Seip syndrome (BSCL) followed at Instituto da Criança, HC-FMUSP. SUBJECTS AND METHODS: Patients with clinical features of BSCL (n = 5), all female, were evaluated through serum levels of glucose, insulin, lipids, leptin, and liver enzymes. Abdominal sonography and DNA analysis were also performed. RESULTS: Leptin deficiency and hypertriglyceridemia were found in all the patients. Three progressed to diabetes mellitus. Four patients have mutations in AGPAT2 gene and one have a mutation in CAV1 gene. CONCLUSION: The earliest metabolic abnormalities were hypertriglyceridemia and insulin resistance, culminating in the onset of diabetes at the time of puberty. Mutations in the AGPAT2 gene were the most frequent in our patients.

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