Background
Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive disease characterized by a near-complete absence of adipose tissue from birth [
1]. This lipodystrophy is associated with fatty liver, hypertriglyceridemia, hyperinsulinemia, type 2 diabetes, acanthosis nigricans, prominent musculature and other clinical conditions [
2‐
5]. It was initially described in 1954 by the Brazilian doctor Waldemar Berardinelli [
1] and in 1959 by the Norwegian doctor Martin Seip [
6].
There are two major subtypes of BSCL: BSCL1 and BSCL2. The molecular cause of the first subtype is a mutation in a gene encoding 1-acylglycerol-3-phosphate
O-acyltransferase 2 (1-AGPAT 2), an enzyme expressed predominantly in adipose tissue that is involved in the biosynthesis of triacylglycerols and phospholipids [
7,
8]. In contrast, BSCL2 is caused by a mutation in a gene encoding seipin, an endoplasmic reticulum transmembrane protein that is involved in adipogenesis and lipid droplet formation [
9,
10]. Although seipin is mainly localized to adipose tissue, it also has functional roles in the testes and brain [
9‐
11].
The prevalences of BSCL in different countries have been established in the medical literature and databanks specializing in rare genetic syndromes [
3,
12,
13]. Although its prevalence worldwide is estimated to be 1 in 12 million people [
12], there is some variation among individuals of different ethnicities. In the US and Norway, the prevalences of this disease are 1 in 10 million and 1 in 1 million people, respectively [
3,
13]. However, in Lebanon, Portugal and Oman, its prevalences are 1 in 200,000, 1 in 500,000 and 1 in 25,000 people, respectively [
13].
Although the first BSCL case was reported in Brazil, its prevalence in this country has not yet been investigated. Limited information is available about the prevalence of BSCL in some regions of Brazil. Previous reports have indicated that cases of this disease have occurred in two regions of Brazil: Rio Grande do Norte (RN) state, located in the northeastern region, and Minas Gerais (MG) state, located in the southeastern region [
14,
15]. Clinical and laboratory data of BSCL patients from RN have recently been reported by Lima and co-workers, revealing that a specific mutation in the BSCL2 gene is predominant in BSCL patients from this state [
16]. Although several cases of BSCL have been reported in RN, there is no information concerning the distribution of cases among the regions and municipalities of RN and Brazil. These data could help establish that Brazil has one of the highest prevalences of BSCL worldwide.
The aim of this study was to estimate the prevalence of BSCL in RN, Brazil, and therefore to provide appropriate epidemiologic data in order to help the Brazilian Health System promote the correct multidisciplinary management of BSCL patients, focusing on genetic counseling for families, prenatal diagnosis and the screening of family members, as well as to improve future studies on this lipodystrophy in Northeast Brazil.
Discussion
Our investigation revealed a high prevalence of BSCL (3.23 in 100,000 inhabitants) in the state of RN, Northeast Brazil. This lipodystrophy affects individuals of all ethnicities, and its worldwide prevalence is estimated to be 1 in 12 million people [
3]. The BSCL prevalences in many countries, such as the US, Norway, Lebanon, Portugal and Oman, have been previously reported [
3,
13]. Cases of this type of congenital lipodystrophy have also been reported in China and Japan [
19,
20].
Our study of BSCL prevalence in RN showed that the Central Potiguar mesoregion had a significantly high prevalence. Unsurprisingly, the Seridó territory, where BSCL cases have been reported in 12 municipalities, is located in the Central Potiguar mesoregion (Table
3). Because Brazil is a developing country with a large area and great socioeconomic and cultural diversity, the regional differences in RN may reveal the specific epidemiological characteristics of BSCL patients.
A preliminary study performed by a mother of a BSCL patient from the Currais Novos municipality showed that consanguineous marriages, which mainly occur in municipalities of the Seridó territory, are responsible for the elevated prevalence of BSCL in RN. This finding has been confirmed by Lima et al. [
16], who verified the frequent occurrence of consanguineous marriages in Seridó, a RN territory where new BSCL cases are diagnosed every year. Thus, a map showing the distribution of BSCL cases among the municipalities of RN can be used to help the government detect new cases of this lipodystrophy, which would allow for the prediction of the health requirements of these patients and the prioritization of the provision of genetic services to affected families from RN as well as those from other Brazilian states.
Although
ASPOBERN did not report the education level of all BSCL patients assisted from 1998 to 2015, we found that several BSCL patients in our study had a low education level. Twenty-one patients (47.7%) had not completed elementary school, 5 patients (11.4%) had completed elementary school, and 3 patients (6.8%) had a higher level of education. According to data obtained from
Instituto Brasileiro de Geografia e Estatística (IBGE), these finding are similar to the socio-demographic data from the northeast population, which showed that 47.6% of Northeast people had not completed elementary school, 9.5% completed elementary school, and 4% had a higher level of education [
21].
Data from the literature indicate that BSCL2 patients have an increased risk of cardiomyopathy and intellectual impairment compared with BSCL1 patients [
22,
23], suggesting that seipin, the protein encoded by the
BSCL2 gene, is involved in the regulation of neuronal functions. Lima et al. have reported that most BSCL patients from RN have a BSCL2 gene mutation, which may be related to the increased incidence of premature death among these patients [
16]. Together, our data concerning the educational levels indicated that the occurrence of the BSCL2 mutation found in RN may not be related to the intellectual profiles of these patients.
Importantly, we analyzed only cases registered by ASPOSBERN, and thus, we may have underestimated the prevalence of BSCL in RN. Another limitation of this study is that we analyzed secondary data; therefore, many important characteristics necessary for evaluating the real prevalence were not collected.
This is the first report of the prevalence of BSCL in Brazil. Because BSCL cases have also been reported in other Brazilian states [
15], the BSCL prevalence that we have reported is an underestimation. The government of the state of RN does not currently report epidemiologic data on BSCL; only
ASPOSBERN has attempted to obtain these data. The potential reasons for the lack of Brazilian BSCL studies are as follows: (i) the large physical size of Brazil; (ii) the absence of a healthcare system that could diagnose BSCL in children; (iii) Brazilian health professionals’ lack of knowledge on BSCL; and (iv) the low number of studies conducted in Brazil concerning Berardinelli-Seip syndrome. Research on BSCL in Brazil is limited compared with that in European countries and the US [
2‐
7,
9,
10,
12,
13,
20,
22,
23].
Our data have indicated that the prevalence of BSCL is high in the state of RN, Brazil. Considering the wide regional diversity and the increasing number of BSCL cases in Brazil, more studies are needed to improve the understanding of its epidemiological characteristics as well as the quality of care provided by clinicians to BSCL patients. Thus, annual reporting of the BSCL prevalence in Brazil is essential for improving the care of BSCL patients, the knowledge of health professionals concerning this type of lipodystrophy, and research on BSCL. Therefore, it is very important to implement an effective system for reporting the prevalence of BSCL in Brazil, which would ultimately help provide direct resources to these patients.
Conclusions
Several cases of BSCL have been reported in RN, but there is no information about the distribution of BSCL among the regions and municipalities of Brazil. Here, we have shown that the BSCL prevalence is high in RN (3.23 per 100,000 people) with emphasis on the Central Potiguar mesoregion, Seridó territory, and Carnaúba dos Dantas and Timbaúba dos Batistas municipalities. Furthermore, most of the patients assisted by ASPOSBERN between 1998 and March 2015 were female adults who had not completed elementary school. The high prevalence of this syndrome highlights the urgent requirement to develop efforts directed at monitoring the incidence of BSCL in Northeast Brazil with a focus on genetic counseling for families. Additionally, more studies are required to better estimate the prevalence and incidence of this condition in additional states of Brazil, which may have important implications for the health care sector.
Authors’ contributions
LBAM and VKCD collected and compiled data. ASCS and JTAMC assisted in writing and formatting the text. All authors assisted with the data analysis. All authors read and approved the final manuscript.