Lipodystrophies in Clinical Practice: A Case Series From a Local Health Unit in Portugal

Background Lipodystrophies are rare disorders characterized by loss of adipose tissue, leading to severe metabolic and multisystem complications. Data on real-world management remain limited, particularly in Portugal. Objectives The objective of this study is to describe the clinical, metabolic, genetic, and therapeutic characteristics of patients with confirmed or suspected lipodystrophy followed at a Portuguese Endocrinology Outpatient Clinic. Methods We conducted a retrospective observational study including 21 patients with clinical suspicion or diagnosis of lipodystrophy. Demographic, clinical, laboratory, imaging, and genetic data were collected. Results The cohort was predominantly female (90.5%) with a median age at diagnosis of 49 years. Sixteen patients (76.2%) had familial partial lipodystrophy (FPLD), two (9.5%) had congenital generalized lipodystrophy, two (9.5%) had acquired generalized lipodystrophy, and one presented a complex syndromic form. Diabetes mellitus was present in 71.4% of patients and hypertriglyceridemia in 52.4%. Metabolic liver disease occurred in both generalized and partial forms. Autoimmune disorders affected 31.6% of patients, and cardiac involvement was observed in 23.8%. Genetic testing identified pathogenic or likely pathogenic variants in BSCL2 and PPARG in three patients, while most FPLD cases remained genetically unexplained. Metreleptin therapy in three patients with generalized lipodystrophy improved glycemic control, triglycerides, liver enzymes, and proteinuria. Dual-energy X-ray absorptiometry imaging supported the phenotypic characterization of adipose tissue loss. Conclusions Detailed physical examination, genetic testing, imaging, and early therapeutic interventions are critical for management. These findings align with European registry data and highlight the need for increased awareness and systematic evaluation in real-world clinical practice.