Lipodystrophies [34 genes]

• Lipodystrophies are a heterogeneous group of rare diseases that are characterized by a generalized or partial absence of adipose tissue. Lipodystrophies predispose to the development of metabolic complications similar to those observed in obesity, which include alterations in lipid metabolism (increase in triglycerides and decrease in HDL), as well as insulin resistance and diabetes mellitus, entities associated with an increase in the risk of premature atherosclerosis.
• The metabolic complications of lipodystrophy are key in morbidity and mortality. Adipose mass deficiency results in leptin deficiency, leading to hyperphagia and ectopic lipid storage, causing insulin resistance. Insulin resistance and associated complications include diabetes mellitus, hypertriglyceridemia, nonalcoholic fatty liver disease, polycystic ovaries, acanthosis nigricans, and premature atherosclerosis.
• Genetically based lipodystrophy includes congenital generalized lipodystrophy (CGL), familial partial lipodystrophy (FLP), and other systemic disorders associated with lipodystrophy such as progeroid lipodystrophy syndromes and autoinflammatory lipodystrophies.

Although genetic testing is not necessary for diagnosis, it is very useful in identifying subtypes of familial lipodystrophies. Additionally, they may help identify family members at risk, especially for lipodystrophy subtypes associated with subtle physical phenotypes or those at high risk for morbidity and mortality (e.g., cardiomyopathy and arrhythmias found in LMNA mutations).

Patients with suspected Congenital Generalized Lipodystrophy (GCL), that is, presence of at least 3 major criteria or 2 major criteria + 2 or more minor criteria. Major criteria include lipoatrophy affecting the trunk, limbs and face, acromegaloid features, hepatomegaly secondary to hepatic steatosis or cirrhosis, elevation of serum triglyceride concentration in some cases associated with hypercholesterolemia, and insulin resistance. Minor criteria include hypertrophic cardiomyopathy, psychomotor delay or mild-moderate cognitive dysfunction, hirsutism, precocious puberty in female patients, bone cysts, prominent veins

Patients with suspected Partial Familial Lipodystrophy (PFL) who present normal fat distribution in childhood, loss of subcutaneous fat in the extremities, trunk and gluteal regions at puberty, redistribution of excess fat to the face, neck, back, labia majora and abdominal cavity or abdominal organs (liver), hepatic steatosis, significant hypertrophy of skeletal muscle fibers, metabolic complications (include hyperlipidemia, hypertriglyceridemia and diabetes), hyperandrogenism, infertility, gestational diabetes, obstetric complications in women.

Patients with suspected progeroid lipodystrophy syndromes or autoinflammatory lipodystrophies.