Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

Background: There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. Objective: This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. Methods: In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. Results: The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. Conclusion: This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Gestational and neonatal outcomes of women with partial Dunnigan lipodystrophy.

Introduction: Lipodystrophies are a group of disorders characterized by selective and variable loss of adipose tissue, which can result in an increased risk of insulin resistance and its associated complications. Women with lipodystrophy often have a high frequency of polycystic ovary syndrome (PCOS) and may experience gynecological and obstetric complications. The objective of this study was to describe the gestational outcomes of patients with familial partial lipodystrophy type 2 (FPLD2) at a reference center with the aim of improving the understanding and management of pregnant women affected by this condition. Methods: This was a retrospective analysis of data obtained from questionnaires regarding past pregnancies and a review of medical records from the beginning of follow-up in outpatient clinics. Results: All women diagnosed with FPLD2 who had previously become pregnant were included in this study (n=8). The women in the study experienced pregnancies between the ages of 14 and 38 years, with an average of 1.75 children per woman. The pregnancies in question were either the result of successful conception within 12 months of attempting to conceive or unplanned pregnancies. During pregnancy, two women (25%) were diagnosed with gestational diabetes mellitus (GDM), one (12.5%) with gestational hypothyroidism, and one (12.5%) with preeclampsia. Among the 17 pregnancies, two miscarriages (11.8%) occurred, and five cases (29.4%) of macrosomia were observed. Four instances of premature birth and an equal number of neonatal hypoglycemia cases were recorded. The reported neonatal complications included an unspecified malformation, respiratory infection, and two neonatal deaths related to heart malformation and respiratory distress syndrome. Conclusion: Our data showed a high frequency of fetal complications in women with FPLD2. However, no instances of infertility or prolonged attempts to conceive have been reported, highlighting the significance of employing effective contraception strategies to plan pregnancies at optimal times for managing metabolic comorbidities.

Waist circumference is independently associated with liver steatosis and fibrosis in LMNA-related and unrelated Familial Partial Lipodystrophy women.

BACKGROUND: Lipodystrophies are a heterogeneous group of diseases characterized by the selective loss of subcutaneous adipose tissue and ectopic fat deposition in different organs, including the liver. This study aimed to determine the frequencies of liver steatosis (LS) and liver fibrosis (LF) in a sample of individuals with LMNA-related and unrelated Familial Partial Lipodystrophy. METHODS: This cross-sectional study included 17 women with LMNA-related FPLD and 15 women with unrelated FPLD. LS and LF were assessed using transient elastography (TE) with FibroScan®. Anthropometric and biochemical variables were included in a multiple linear regression analysis to identify the variables that were independently related to liver disease. RESULTS: Regarding the presence of LF, 22 (68.2%) women were classified as having non-significant fibrosis, and 10 (31.8%) were classified as having significant or severe fibrosis. Regarding LS, only six women (20.7%) were classified as having an absence of steatosis, and 23 (79.3%) had mild to severe steatosis. After multiple linear regression, waist circumference (but not age, body mass index, or waist-to-hip ratio) was found to be independently related to LS and LF. Among the biochemical variables, only triglyceride levels were independently related to LS but not LF. CONCLUSIONS: In women with FPLD, visceral fat accumulation appears to be the most important determinant of liver disease, including LF, rather than fat scarcity in the lower limbs.