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Disease Profile

Congenital generalized lipodystrophy

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Brunzell syndrome; BSCL; GCL;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Skin Diseases

Summary

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).[1][2]

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.[3][1][2] 

The inheritance of Berardinelli-Seip congenital lipodystrophy is autosomal recessive.[1] Treatment consists on a fat restricted diet and diabetes control, and may also include leptin administration.[3][2]

 

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Adipose tissue loss
Loss of fat tissue
0008887
Hepatomegaly
Enlarged liver
0002240
Insulin resistance
Body fails to respond to insulin
0000855
Lipodystrophy
Inability to make and keep healthy fat tissue
0009125
30%-79% of people have these symptoms
Diabetes mellitus
0000819
Hypertrichosis
0000998
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides

[ more ]

0002155
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
5%-29% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Acanthosis nigricans
Darkened and thickened skin
0000956
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Bone cyst
Bone cysts
0012062
Cirrhosis
Scar tissue replaces healthy tissue in the liver
0001394
Clitoral hypertrophy
Enlarged clitoris
0008665
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Global developmental delay
0001263
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Hypercholesterolemia
Elevated serum cholesterol
Elevated total cholesterol
Increased total cholesterol

[ more ]

0003124
Hyperinsulinemia
0000842
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Increased Cpeptide level
0030796
Large hands
large hand
0001176
Long foot
Disproportionately large feet
large feet
long feet

[ more ]

0001833
Low anterior hairline
Low frontal hairline
Low-set frontal hairline

[ more ]

0000294
Low posterior hairline
Low hairline at back of neck
0002162
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue

[ more ]

0000158
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Overgrowth of external genitalia
0003247
Prominent superficial veins
Prominent veins
0001015
Prominent supraorbital ridges
Prominent brow
0000336
Proportionate tall stature
0011407
Psychomotor retardation
0025356
1%-4% of people have these symptoms
Amenorrhea
Abnormal absence of menstruation
0000141
Oligomenorrhea
Light or infrequent menstrual periods
0000876
Polycystic ovaries
0000147
Precocious puberty in females
0010465

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Congenital generalized lipodystrophy in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

  1. Berardinelli-Seip. Genetics Home Reference. 2016; https://ghr.nlm.nih.gov/condition/berardinelli-seip-congenital-lipodystrophy.
  2. Maldergem LV. Berardinelli-Seip Congenital Lipodystrophy. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK1212/.
  3. Monajemi H, Stroes E, Hegele RA, and Fliers E. Inherited Lipodystrophies and the Metabolic Syndrome. Clin Endocrinol. 2007; 67(4):479-484. https://www.medscape.com/viewarticle/564557_3.