PLIN1-related familial partial lipodystrophy

PLIN1-related familial partial lipodystrophy (also known as familial partial lipodystrophy type 4, or FPLD4) is a rare genetic disorder caused by mutations in the PLIN1 gene, which encodes perilipin-1, a protein that coats lipid droplets in adipocytes and plays a critical role in regulating fat storage and breakdown. This condition is characterized by the progressive loss of subcutaneous adipose tissue (fat beneath the skin), particularly from the limbs and trunk, typically beginning in adulthood. Affected individuals may retain or accumulate fat in other areas, such as the face and neck, leading to an abnormal distribution of body fat. The metabolic consequences of this lipodystrophy are significant. Because the body cannot properly store fat in subcutaneous tissue, lipids accumulate in organs such as the liver and muscles, leading to insulin resistance, type 2 diabetes mellitus, hypertriglyceridemia (elevated blood triglycerides), hepatic steatosis (fatty liver disease), and an increased risk of cardiovascular disease. Women may also experience features such as polycystic ovary syndrome, hirsutism, and menstrual irregularities. Some patients develop acanthosis nigricans, a darkening and thickening of the skin in body folds, which is a marker of insulin resistance. There is currently no cure for PLIN1-related familial partial lipodystrophy. Treatment focuses on managing the metabolic complications through dietary modifications (particularly a low-fat diet), regular physical activity, and pharmacological interventions including lipid-lowering agents, insulin sensitizers such as metformin or thiazolidinediones, and insulin therapy when diabetes develops. In select cases of severe metabolic derangement, metreleptin (recombinant leptin) therapy may be considered if leptin deficiency is documented, though its availability varies by region. Close monitoring by a multidisciplinary team including endocrinologists, cardiologists, and hepatologists is recommended.

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