Berardinelli-Seip congenital lipodystrophy

Berardinelli-Seip congenital lipodystrophy is a rare condition characterized by a lack of fatty (adipose) tissue in the body. This lack of adipose tissue means that fats must be stored elsewhere in the body, such as in the liver and muscles. The abnormal handling and storage of fats leads to serious medical problems.

The signs and symptoms of Berardinelli-Seip congenital lipodystrophy are apparent from birth or early infancy. Common features of this disorder include high levels of fats (triglycerides) circulating in the bloodstream (hypertriglyceridemia) and insulin resistance, a condition in which the body's tissues are unable to recognize insulin. Insulin is a hormone that helps regulate blood sugar levels. During adolescence, insulin resistance may develop into a more serious disease called diabetes mellitus. Berardinelli-Seip congenital lipodystrophy also causes an abnormal buildup of fats in the liver (hepatic steatosis), which can damage this organ. An accumulation of fats in the heart can cause a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and sudden death.

People with Berardinelli-Seip congenital lipodystrophy have a distinctive physical appearance. The combination of an almost total absence of adipose tissue and an overgrowth of muscle tissue makes these individuals appear very muscular. They also tend to have a large chin, prominent bones above the eyes (orbital ridges), and large hands and feet. Affected females may have an enlarged clitoris (clitoromegaly), and males also tend to have enlarged external genitalia. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.

Researchers have described two similar forms of Berardinelli-Seip congenital lipodystrophy, type 1 and type 2, which are distinguished by their genetic cause. The two types also have a few differences in their typical signs and symptoms. For example, in addition to the features described above, some people with type 1 develop bone cysts in the long bones of the arms and legs after puberty. Type 2 is frequently associated with intellectual disability, which is usually mild to moderate. Intellectual disability is occasionally seen with type 1, although it is much less common.

Berardinelli-Seip congenital lipodystrophy has an estimated prevalence of 1 in 10 million people worldwide. Although this condition has been reported in populations around the world, it may be more common in certain regions of Lebanon, Brazil, and Portugal.

Mutations in the AGPAT2 and BSCL2 genes cause the two types of Berardinelli-Seip congenital lipodystrophy. AGPAT2 mutations are responsible for type 1, while mutations in BSCL2 cause type 2.

The proteins produced from the AGPAT2 and BSCL2 genes play important roles in adipocytes, which are the fat-storing cells in adipose tissue. Mutations in either of these genes disrupt the normal development or function of adipocytes, preventing normal adipose tissue from forming. As a result, the body is unable to use and store fats properly. An almost total absence of body fat underlies the varied signs and symptoms of Berardinelli-Seip congenital lipodystrophy.

The protein produced from the BSCL2 gene is also present in the brain and testes, although its function in these tissues is unknown. A loss of this protein in the brain may help explain why many people with Berardinelli-Seip congenital lipodystrophy type 2 have intellectual disability.

In some people with Berardinelli-Seip congenital lipodystrophy, no mutation in the AGPAT2 or BSCL2 gene has been found. Researchers are searching for additional genetic changes that may cause this disorder.

Read more about the AGPAT2 and BSCL2 genes.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.