Causes of death in patients with Berardinelli-Seip congenital generalized lipodystrophy.

INTRODUCTION: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease that affects the development of adipocytes and leads to an inability to store fat in adipocytes. This study aimed to evaluate the life expectancy and the causes of death of patients with BSCL. METHOD: We analyzed death certificates, and medical records of BSCL patients who died between 1997 and 2017. If the death certificate was incomplete or unavailable, we reviewed the medical records, and if they were not available too, we collected information from the patient's relatives to understand how the death happened. We calculated the potential years of life lost as a result of premature death. RESULTS: Twenty patients (12 female and 8 male) died between 1997 and 2017. The mean age at the time of death was 27.1±12.4 years (women 25.2±12.5 vs. men 29.9±12.6 years, p = 0.41). Life expectancy for the study population was 62.9±4.8 years. The potential number of years of life lost was 35.6±16.6 years. The causes of deaths were divided into three major groups: infections (7 patients, 35%), liver disease (7 patients, 35%), and other causes (acute pancreatitis, one patient; renal failure, three patients; sudden death/myocardial infarction, two patients). Three patients had pulmonary fibrosis. CONCLUSION: BSCL led to premature death, cutting the patients' lifespan by 30 or more years. The majority of these young patients died of liver disease or infection. Other studies are needed to understand better the mechanisms that predispose to infections, as well as to assess whether new therapies can alter the natural history of this disease.

Bone Density in Patients With Berardinelli-Seip Congenital Lipodystrophy Is Higher in Trabecular Sites and in Type 2 Patients.

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.

Normal bone density and trabecular bone score, but high serum sclerostin in congenital generalized lipodystrophy.

CONTEXT: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/ß-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. OBJECTIVE: We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients. DESIGN, SETTING, AND PATIENTS: In this cross-sectional study, we included 11 diabetic patients with BSCL (age 24.7±8.1years; 6 females). Sclerostin, leptin, L1-L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested. RESULTS: Mean serum sclerostin was elevated (44.7±13.4pmol/L) and was higher in men than women (55.3±9.0 vs. 35.1±8.4pmol/L, p=0.004). Median of serum leptin was low [0.9ng/mL (0.5-1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score>+2.5SD). Patients on insulin had lower sclerostin (37.3±9.2 vs. 52.6±13.4pmol/L, p=0.05). The mean TBS was 1.402±0.106, and it was higher than 1.300 in nine patients. CONCLUSIONS: Patients with lipoatrophic diabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin and good bone microarchitecture (TBS) in BSCL patients.

Conversations between insulin and bone: Potential mechanism of high bone density in patients with Berardinelli-Seip Congenital Lipodystrophy.

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty storing lipid in adipocytes, low body fat, hypertriglyceridemia, and fat liver. The serum leptin is usually very low, and serum insulin, as well as HOMAIR (homeostasis model assessment), is very high and correlated positively with bone mineral density (BMD). Despite deficiency/insufficiency of vitamin D, low body mass index, low daily calcium intake, physical inactivity, and menarche at a later age, BSCL patients usually have normal or even high BMD. We hypothesize that low leptin and high insulin may play a role in this outcome. Understanding the potential pathophysiological mechanism of these bone abnormalities will help to clarify the effects of extreme insulin resistance in the bone.

Clinical and laboratory data of a large series of patients with congenital generalized lipodystrophy.

BACKGROUND: Berardinelli-Seip congenital lipodystrophy (BSCL) was initially described by Berardinelli in Brazil in 1954 and 5 years later by Seip in Norway. It is an autosomal recessive disease that leads to a generalized deficit of body fat, evolving with diabetes and hypertriglyceridemia. The aim of this study was to describe the clinical and laboratory characteristics of a large series of patients with BSCL. METHODS: This is a cross-sectional study of patients with BSCL. A total of 54 cases of BSCL were diagnosed, treated and followed for the past 17 years. We report clinical and laboratorial data of 44 of those patients. RESULTS: There was a predominance of female patients (27 patients), and the mean age was 21.3 ± 13.7 years old. The majority of patients (30/44; 68.2 %) were diabetic, and almost half of them (14/30 patients, 46.7 %) were on insulin. The mean body mass index was 19.6 ± 3.3 and the mean body fat measured by dual-energy X-ray absorptiometry (DEXA) was 5.4 ± 0.8 %. Acanthosis nigricans, acromegaloid facies, atrophic cheeks, prognathism, phlebomegaly, and muscle hypertrophy were the most common clinical features. Only two patients had triglyceridemia lower than 150 mg/dl without the use of lipid-lowering drugs. Hyperinsulinemia was present in the majority of patients, and leptin values were very low in all patients. CONCLUSIONS: We report one of the largest series of patients with BSCL treated at a single medical center. Earlier identification of the mutations and a better understanding of the pathophysiology can aid to better treatment and decrease complications, potentially improving life quality and expectancy.

Fatores associados com recidiva precoce do hipertireoidismo após tratamento com radioiodoterapia / Factors associated to early recurrence of hyperthyroidism following 131I therapy

OBJETIVOS: Avaliar os fatores associados com persistência ou recorrência do hipertireoidismo após tratamento com131 I. METODOLOGIA: Análise retrospectiva de prontuários de todos os pacientes com hipertireoidismo tratados com dose fixa de 400MBq de131 I em um centro especializado (1992 a 1997). Dos 104 pacientes tratados nesse período, seis tinham bócio multinodular e um adenoma tóxico; 96 estavam usando tionamidas que foram descontinuadas 7 dias antes da administraçäo do iodo. RESULTADOS: Progressäo precoce para hipotireoidismo ocorreu em mediana de 88 dias (22-214) em 60 pacientes (57,7 por cento). Persistência ou recorrência do hipertireoidismo ocorreu em 13 pacientes (12,5 por cento) e foram relacionadas positivamente com a idade (p<0,007), embora näo relacionadas com o diagnóstico. Houve maior prevalência de doença persistente nos pacientes tratados com propiltiouracil previamente ao radioiodo do que naqueles tratados com carbimazol (35 por cento vs. 8 por cento; p<0,006). CONCLUSÕES: O efeito bloqueador das tionamidas na captaçäo do radioiodo parece ser mais prolongado em idosos. O efeito radioprotetor do propiltiouracil parece ser mais duradouro que o do carbimazol.