Lipodystrophic syndromes and Partial lipodystrophy

Lipodystrophic syndromes––acquired or genetic––are rare diseases marked by a generalized or partial absence of adipose tissue. These lead to significant metabolic disturbances – linked to severe insulin resistance. However, these conditions remain underdiagnosed, particularly in their partial forms. 

Lipodystrophic syndromes are characterized by insufficient adipose tissue development, resulting in metabolic disorders such as – severe insulin resistance, hypertriglyceridemia, and hepatic steatosis. In partial lipodystrophy, these issues are exacerbated by excess visceral and/or subcutaneous fat in the upper body. 

Diagnosis involves – clinical examination, consideration of pathological context and comorbidities, metabolic investigations, and genetic analyses––which collectively inform management and genetic counseling. Early intervention with – lifestyle and dietary modifications, emphasizing regular physical activity and a balanced diet avoiding excess caloric intake, is essential. These measures are supported by multidisciplinary follow-up tailored to each clinical presentation. 

When standard treatments fail to manage metabolic disorders, metreleptin––an orphan drug and leptin analog––may be effective for certain lipodystrophy forms.

In partial lipodystrophy, particularly in women, abnormal fat distribution is prominent, with lipoatrophic areas coexisting with fat accumulation zones. In familial partial lipodystrophy (FPLD), particularly the Dunnigan type (FPLD2) caused by LMNA gene variants, limb lipoatrophy is accompanied by facio-cervical adiposity, including a round face, double chin, supraclavicular fullness, and a "buffalo hump." Metabolic investigations often reveal hypertriglyceridemia, low HDL cholesterol, hyperinsulinemia, glucose tolerance abnormalities or diabetes, and elevated liver enzymes indicative of hepatic steatosis. An oral glucose tolerance test can be helpful in diagnosis by showing post-stimulatory hyperinsulinemia or impaired glucose tolerance. Elevated circulating creatine phosphokinase levels – indicating muscle damage, and ovarian-origin hyperandrogenism are also observed.

A family history of lipodystrophy or atypical diabetes, severe dyslipidemia, spontaneous muscle hypertrophy, or hyperandrogenism in women suggests an autosomal form of lipodystrophy. When FPLD is suspected, patients are referred to specialists for sequencing the LMNA gene or other relevant genes. Genetic diagnosis is crucial for understanding specific comorbidities, improving disease management, and identifying affected relatives.

Partial lipodystrophy syndromes are linked with various cardiometabolic complications. No current therapies can restore adipose tissue function in lipoatrophic areas, so treatment focuses on managing complications through dietary measures to prevent excess caloric intake and increasing physical activity to enhance insulin sensitivity. Pharmaceutical treatments may include hypolipidemic drugs like statins and fibrates. Thorough clinical examination and investigation of cardiometabolic abnormalities are fundamental for diagnosis, and genetic diagnosis can guide the identification of specific comorbidities and improve disease management. Early intervention is critical for managing metabolic complications effectively.

Source: Mosbah H, Vatier C, Vigouroux C. Ann Endocrinol (Paris). 2024;85(3):197-200.