Familial partial lipodystrophy, Dunnigan type

Familial partial lipodystrophy, Dunnigan type (FPLD2), also known as Köbberling-Dunnigan syndrome or familial partial lipodystrophy type 2, is a rare genetic disorder characterized by the progressive loss of subcutaneous adipose tissue (fat) from the limbs, trunk, and gluteal region, typically beginning around puberty. The condition is caused by mutations in the LMNA gene, which encodes lamin A/C, a structural protein of the nuclear envelope. Affected individuals, particularly females, tend to accumulate excess fat in the face, neck, and intra-abdominal region, giving a cushingoid appearance. The disease predominantly affects women more severely than men due to hormonal influences on fat distribution. The metabolic consequences of FPLD2 are significant and include severe insulin resistance, type 2 diabetes mellitus, hypertriglyceridemia, low HDL cholesterol, hepatic steatosis (fatty liver), and an increased risk of acute pancreatitis due to markedly elevated triglycerides. Women may also develop polycystic ovary syndrome, hirsutism, and menstrual irregularities. Acanthosis nigricans, a darkening and thickening of the skin in body folds, is commonly observed. Cardiovascular complications, including premature atherosclerosis and cardiomyopathy, represent major sources of morbidity and mortality. There is no cure for FPLD2, and management focuses on controlling metabolic complications. Treatment includes dietary modifications (particularly a low-fat diet), exercise, and pharmacological interventions such as metformin, thiazolidinediones, fibrates, and statins to manage diabetes and dyslipidemia. Metreleptin (recombinant human leptin) has been approved for the treatment of metabolic complications in patients with generalized and partial lipodystrophy who have leptin deficiency, and has shown significant benefit in improving glycemic control and reducing triglyceride levels. Regular monitoring for cardiovascular disease, liver disease, and pancreatitis is essential.

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