Congenital Generalized Lipodystrophy (GCL)

External Ids:

Disease Ontology 12 DOID:0050585 KEGG 36 H00419

EFO 17 EFO_1000681 UMLS 71 C0011859 C0221032 C1720860 C1720863 more

Genetics Home Reference : ²⁵ Congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) is a rare condition characterized by an almost total lack of fatty (adipose) tissue in the body and a very muscular appearance. Adipose tissue is found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat for energy and also provides cushioning. Congenital generalized lipodystrophy is part of a group of related disorders known as lipodystrophies, which are all characterized by a loss of adipose tissue. A shortage of adipose tissue leads to the storage of fat elsewhere in the body, such as in the liver and muscles, which causes serious health problems. The signs and symptoms of congenital generalized lipodystrophy are usually apparent from birth or early childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are unable to recognize insulin, a hormone that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called diabetes mellitus. Most affected individuals also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to the development of small yellow deposits of fat under the skin called eruptive xanthomas and inflammation of the pancreas (pancreatitis). Additionally, congenital generalized lipodystrophy causes an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and liver failure. Some affected individuals develop a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and an abnormal heart rhythm (arrhythmia) that can cause sudden death. People with congenital generalized lipodystrophy have a distinctive physical appearance. They appear very muscular because they have an almost complete absence of adipose tissue and an overgrowth of muscle tissue. A lack of adipose tissue under the skin also makes the veins appear prominent. Affected individuals tend to have prominent bones above the eyes (orbital ridges), large hands and feet, and a prominent belly button (umbilicus). Affected females may have an enlarged clitoris (clitoromegaly), an increased amount of body hair (hirsutism), irregular menstrual periods, and multiple cysts on the ovaries, which may be related to hormonal changes. 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 four types of congenital generalized lipodystrophy, which are distinguished by their genetic cause. The types also have some differences in their typical signs and symptoms. For example, in addition to the features described above, some people with congenital generalized lipodystrophy type 1 develop cysts in the long bones of the arms and legs after puberty. Type 2 can be associated with intellectual disability, which is usually mild to moderate. Type 3 appears to cause poor growth and short stature, along with other health problems. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, a narrowing of the lower part of the stomach (pyloric stenosis), and severe arrhythmia that can lead to sudden death.

MalaCards based summary : Congenital Generalized Lipodystrophy, also known as berardinelli-seip congenital lipodystrophy, is related to lipodystrophy, congenital generalized, type 4 and lipodystrophy, congenital generalized, type 3, and has symptoms including myalgia An important gene associated with Congenital Generalized Lipodystrophy is AGPAT2 (1-Acylglycerol-3-Phosphate O-Acyltransferase 2), and among its related pathways/superpathways are Glycerophospholipid biosynthesis and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). The drugs Propoxycaine and Proxymetacaine have been mentioned in the context of this disorder. Affiliated tissues include heart, liver and bone, and related phenotypes are behavior/neurological and adipose tissue

Disease Ontology : ¹² A lipodystrophy that is characterized by extreme scarcity of subcutaneous fat, muscular hypertrophy, fatty liver, hypertriglyceremia and metabolic complications including insulin resistance.

NIH Rare Diseases : ⁵² Congenital generalized lipodystrophy is a rare disease characterized by a generalized lack of fat (adipose tissue ) in the body. It is part of a group of diseases known as lipodystrophies. Signs and symptoms are noticed from birth (congenital) or early childhood and include high levels of fats (triglycerides) in the blood (hypertriglyceridemia) and insulin resistance (in which the body tissues are unable to respond to the hormone insulin that helps to regulate blood sugar levels) resulting in diabetes mellitus , abnormal accumulation of fat in the liver (liver steatosis) and the accumulation of fat in the heart causing a thickening of the heart muscle (hypertrophic cardiomyopathy ), which can lead to a heart that does not work well (heart failure) and sudden death. Due to the almost total absence of fatty tissue and excessive growth of muscle tissue, the patients appear very muscular and have visible and prominent veins. They also have dark and thick skin in the body folds (acanthosis nigricans ). There are 4 types of the disease that are distinguished by the altered (mutated ) genes and by some additional characteristic symptoms. People with type 1, caused by mutations in the AGPAT2 gene, may have cysts in the long bones of the arms and the legs after puberty. In type 2, which is caused by mutations in the BSCL2 gene, there may be intellectual disability . In type 3, caused by mutations in the CAV1 gene, affected people may have short stature and growth delay. Type 4, caused by mutations in the CAVIN1 gene, is associated with muscle weakness, developmental delay , joint anomalies, narrowing of the lower part of the stomach (pyloric stenosis), and severe heart arrhythmia that can lead to sudden death. The inheritance of Berardinelli-Seip congenital lipodystrophy is autosomal recessive . Treatment consists on a fat restricted diet and diabetes control, and may also include leptin administration.

KEGG : ³⁶ Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease characterized by near total absence of adipose tissue from birth. Several metabolic alterations in carbohydrate (diabetes mellitus) and lipid metabolism and involvement of heart, bone and ovaries are also observed in this disease. Patients typically have low serum levels of leptin and adiponectin. Several genes were studied to identify the molecular alteration responsible for CGL, which have been found to contribute to lipid droplet formation in adipocytes.

Wikipedia : ⁷⁴ Congenital generalized lipodystrophy (also known as Berardinelli-Seip lipodystrophy) is an extremely... more...

Search NIH Clinical Center for Congenital Generalized Lipodystrophy

Search GEO for disease gene expression data for Congenital Generalized Lipodystrophy.