Heterogeneidade fenotípica e genética em pacientes com lipodistrofia parcial familiar identificados no Ceará

Abstract

Lipodystrophy is characterized by changes in body fat deposits. They are classified according to the extent of fat loss (generalized or partial) and the form of inheritance (inherited or acquired). Family partial lipodystrophy (PFL) are rare forms characterized by distribution of centripetal body adiposity, diabetes mellitus (DM) in this way often diagnosed clinically only as metabolic syndrome. The diversity of characteristics of the genetically defined subtypes of LPF is still the subject of investigation and there is no described series of this disease in northeastern Brazil. This study aimed to describe the clinical phenotypic characteristics of patients with LPF with positive genotype, identified in Ceará. This is a cross-sectional study in which clinical records were analyzed the clinical records of patients with genetic diagnosis of PFL under follow-up in the Hospital Complex of Universidade Federal do Ceará (UFC) /Ebserh from 2002 to 2022. Sociodemographic and clinical data were obtained, in addition to physical examination and anthropometry findings, being analyzed according to the PFL subtypes and mutations identified. Results: Forty-four patients with PFL were identified in follow-up, of which 16 patients had a positive genetic diagnosis. These patients had a median age of 35.5 years (23-67), with a predominance of women (15). Fourteen patients (87.5%) had mutation in the LMNA gene (type 2 PFL) and two (12.5%) mutation in the PPARG gene (ype 3 PFL). Among those with mutation in the LMNA gene, two (12.5%) presented genetic variant in homozygosis (p.R582) and the other in heterozygosis, with changes in the codons p.Arg482 (18.7%) and p.Arg582 (56.2%). Consanguinity was reported by 4 patients (25.0%). The perception of change in body fat pattern was at 20 years (9-65). Body mass index (BMI) was 25.5 kg/m2 (19.0-36.1), with a high prevalence of eutrophic patients (43.7%).The skinfold thickness was 7mm (4-19) in women, and 11mm in the only man in the sample. The index between adiposity in the upper and lower body (Fat Mass Ratio - FMR) was 1.58 (1,01-2,15). The comorbidities most associated with PFL in this sample were: hypertriglyceridemia (93.7%), liver disease (75.0%), DM (68.7%) and SAH (43.7%). Inadequate metabolic control was quite prevalent (81.8%), with glycohemoglobin A1c> 8% (6.3-13.9), despite the use of high doses of insulin, with a daily dose of 2.05 IU/kg/day (0.79-3.8). Complications related to DM, retinopathy, kidney disease and polyneuropathy were present in 18.1%, 27.2% and 63.6%, respectively. Despite the prevalent severe hypertriglyceridemia, no patient evolved with pancreatitis. One patient evolved into liver failure and liver transplantation. Conclusion: This is a large series of cases of this rare disease, being the first description of LPF of this magnitude 10 of northeastern Brazil where there was an important heterogeneity of the phenotype and genotype. However, mutations in the LMNA p.Arg582, p.R582 gene were the most prevalent; and difficult-to-control metabolic comorbidities (DM and hypertriglyceridemia) were commonly associated. Skinfold measurements in the thigh and the MrF proved to be important clinical markers of the disease.