Crescimento, desenvolvimento puberal e estatura final de indivíduos com Lipodistrofia Generalizada Congênita

Abstract

Growth is the result of multiple interactions between genetics, hormones, nutritional and environmental factors and health conditions, being an excellent indicator of health. Puberty characterizes the transition from childhood to adulthood, a period in which growth acceleration and consolidation occurs. Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by the total or almost total absence of adipose tissue from the first years of life and by severe hormonal and metabolic changes that can affect linear growth and pubertal development. However, data on such aspects in individuals with CGL are scarce in the literature. Thus, the objective of this study was to describe the pattern of pubertal growth and development and final height of a large series of individuals with CGL. Methods: This is a retrospective study, in which the clinical records of all patients with CGL in follow-up at the Complexo Hospitalar da Universidade Federal do Ceará (UFC)/Ebserh, from 2002 to 2022, were analyzed. Anthropometric and pubertal development data were obtained from all children and adolescents with CGL in follow-up, with clinical diagnosis and confirmation with genetic study. Results: Data from 26 patients, 18 (69%) of type 1, due to mutations in the AGPAT2 gene (CGL1) and 8 (31%) of type 2, with mutations in the BSCL2 gene (CGL2). Of these, 15 were children/adolescents and 11 adults with LCG. The age at diagnosis of CGL was 0.50 years [0.08- 4.25]. The age at diagnosis of CGL was 0.50 years [0.08-4.25]. The median follow-up time was 11.7 years [1.2-21.1], with the longest follow-up being 21.1 years. The median age at the first consultation was 0.75 years [0.5-6.75] and the age at the last follow-up was 12.2 years [1.7- 22.7]. All patients had severe hypoleptinemia [0.2-1.9 ng/ml] and insulin resistance, with a HOMA-IR of 4.9 [3.8-30.9], and insulinemia of 28.0 mIU/mL [15.8-118.1]. Acanthosis nigricans was evident in 11 cases (73%) since 1.3 years [0.7-7.0]. The diagnosis of DM occurred at 8 years of age [0.2-13]. Birth weight and length were 3.4 kg [1.0-3.8] and 50 cm [38-53] respectively. The growth velocity (GV) in the first 2 years was evaluated in 7 children, being 31.0 cm [24.2-42.0] from birth to 1 year and 14.3 cm [8.2-20.0] between 1 and 2 years of age. The height curve of these individuals followed the equivalent of 2 standards deviations (WHO) up to 7 years in boys and 10 years in girls. In both sexes, GV was increased between 2 and 5 years of age, with deceleration after 6 years of age and with the absence of the pubertal spurt. All girls had early thelarche - 6.7 years [5.1-7.7], however with a delay in the age of menarche - 15 years [12-19]. Final height was 171.5 cm [162–176] in men and 161.0 cm [153.0-165.5] in women. Conclusion: This study characterizes in an unprecedented way the growth, pubertal development and final height of patients with congenital generalized lipodystrophy, based on data from a large series of a single Brazilian reference center in Ceará. These results suggest that the pattern of pubertal growth and development in CCL is atypical, characterized by early thelarche and late menarche in girls, and with accelerated growth velocity in the first 2 years of life, with subsequent deceleration and absence of pubertal spurt, but reaching normal final height in both sexes. It is possible that the rapid growth of the first years of life contributes to such a final outcome of height, within the normal range. Prospective multicenter studies will be needed to confirm these findings and possible mechanisms involved.