SNP Shot: Genomic Insights

Familial partial lipodystrophy (FPLD) is a rare disorder characterized by an unusual distribution of body fat, also known as adipose tissue. Normally, adipose tissue is present throughout the body, including under the skin and around internal organs. It serves as an energy reserve and provides cushioning. In individuals with FPLD, there is a loss of adipose tissue from the arms, legs, and hips, leading to a more muscular appearance in these areas. However, fat that cannot be stored in these limbs accumulates in the face, neck, and abdomen. This excess fat can give the individual a "cushingoid" appearance, similar to the features seen in Cushing disease, a hormonal disorder. The onset of this abnormal fat distribution can vary from childhood to adulthood.

The unusual fat storage patterns in FPLD can trigger various health complications later in life. A common issue is insulin resistance, where the body's tissues don't respond effectively to insulin, a hormone crucial for regulating blood sugar (glucose) levels. If insulin resistance worsens, it can develop into diabetes mellitus. Some individuals with FPLD also experience acanthosis nigricans, a skin condition linked to elevated insulin levels. This condition causes the skin in body folds and creases to become thickened, darkened, and velvety.

Hypertriglyceridemia, or elevated levels of triglycerides (a type of fat) in the bloodstream, is often observed in individuals with FPLD. This can lead to pancreatitis, or inflammation of the pancreas. FPLD can also lead to hepatic steatosis, the accumulation of fat in the liver, which may result in hepatomegaly (enlarged liver) and impaired liver function. After puberty, some women with FPLD may develop polycystic ovaries, increased body hair (hirsutism), and infertility, potentially due to hormonal imbalances.

At least six different forms of FPLD have been identified, each linked to a specific genetic mutation. Type 2 FPLD, also known as Dunnigan disease, is the most prevalent form. In addition to the symptoms mentioned above, some individuals with type 2 FPLD may experience muscle weakness (myopathy), heart muscle abnormalities (cardiomyopathy), coronary artery disease, and problems with the heart's electrical conduction system.

Inheritance:

Most cases of FPLD, including type 2, are inherited in an autosomal dominant manner. This means that only one copy of the mutated gene is needed in each cell to cause the disorder. An affected individual may inherit the mutation from an affected parent. In other cases, the mutation occurs spontaneously, with no prior family history of the disorder. Less commonly, FPLD can be inherited in an autosomal recessive pattern, where both copies of the gene in each cell must be mutated. In this scenario, each parent carries one copy of the mutated gene, but they usually do not exhibit symptoms of the condition.