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Congenital generalized lipodystrophy

MedGen UID:
67438
Concept ID:
C0221032
Disease or Syndrome; Finding
Synonym: Congenital generalized lipodystrophy (disease)
SNOMED CT: Lawrence syndrome (86907008); Lipoatrophic diabetes mellitus (284449005); Total lipoatrophy (284449005); Berardinelli-Seip congenital lipodystrophy (284449005); Congenital generalized lipodystrophy (284449005); Beradinelli-Seip syndrome (284449005); Berardinelli's syndrome (284449005); Lawrence-Seip syndrome (284449005); Seip's syndrome (284449005); Congenital total lipodystrophy (284449005)
 
Related genes: CAVIN1, BSCL2, AGPAT2, CAV1
 
HPO: HP:0009059
Monarch Initiative: MONDO:0006536
OMIM® Phenotypic series: PS608594

Disease characteristics

Excerpted from the GeneReview: Berardinelli-Seip Congenital Lipodystrophy
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality. [from GeneReviews]
Authors:
Lionel Van Maldergem   view full author information

Additional description

From MedlinePlus Genetics
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.

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.

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 levels of blood glucose, also called blood sugar. 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.  https://medlineplus.gov/genetics/condition/congenital-generalized-lipodystrophy

Conditions with this feature

Lipodystrophy-intellectual disability-deafness syndrome
MedGen UID:
334166
Concept ID:
C1842465
Disease or Syndrome
Lipodystrophy-intellectual disability-deafness syndrome is an extremely rare form of genetic lipodystrophy (see this term), reported in 3 patients from one family to date, characterized by generalized congenital lipodystrophy, low birth weight, progressive sensorineural deafness occurring in childhood, intellectual deficit, progressive osteopenia, delayed skeletal maturation, skeletal abnormalities described as slender, undermineralized tubular bones, and dense metaphyseal striations in the distal femur, ulna and radius of older patients. Autosomal recessive inheritance has been suggested.

Professional guidelines

PubMed

Patni N, Chard C, Araújo-Vilar D, Phillips H, Magee DA, Akinci B
Orphanet J Rare Dis 2024 Jul 11;19(1):263. doi: 10.1186/s13023-024-03245-3. PMID: 38992753Free PMC Article
Gupta N, Asi N, Farah W, Almasri J, Barrionuevo P, Alsawas M, Wang Z, Haymond MW, Brown RJ, Murad MH
J Clin Endocrinol Metab 2017 Feb 1;102(2):363-374. doi: 10.1210/jc.2016-2271. PMID: 27967300Free PMC Article
Jéru I, Vatier C, Araujo-Vilar D, Vigouroux C, Lascols O
Eur J Hum Genet 2016 Nov;24(11) Epub 2016 May 18 doi: 10.1038/ejhg.2016.53. PMID: 27189019Free PMC Article

Recent clinical studies

Etiology

Akinci G, Alyaarubi S, Patni N, Alhashmi N, Al-Shidhani A, Prodam F, Gagne N, Babalola F, Al Senani A, Muniraj K, Elsayed SM, Beghini M, Saydam BO, Allawati M, Vaishnav MS, Can E, Simsir IY, Sorkina E, Dursun F, Kamrath C, Cavdar U, Chakraborty PP, Dogan OA, Al Hosin A, Al Maimani A, Comunoglu N, Hamed A, Huseinbegovic T, Scherer T, Curtis J, Brown RJ, Topaloglu H, Simha V, Wabitsch M, Tuysuz B, Oral EA, Akinci B, Garg A
Am J Med Genet A 2024 Jun;194(6):e63533. Epub 2024 Jan 17 doi: 10.1002/ajmg.a.63533. PMID: 38234231Free PMC Article
Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, Araújo-Vilar D
Front Endocrinol (Lausanne) 2023;14:1250203. Epub 2023 Nov 16 doi: 10.3389/fendo.2023.1250203. PMID: 38034001Free PMC Article
Patni N, Garg A
Curr Diab Rep 2022 Sep;22(9):461-470. Epub 2022 Jul 11 doi: 10.1007/s11892-022-01485-w. PMID: 35821558Free PMC Article
Mainieri F, Tagi VM, Chiarelli F
Front Endocrinol (Lausanne) 2022;13:879979. Epub 2022 May 4 doi: 10.3389/fendo.2022.879979. PMID: 35600578Free PMC Article
Sorkina E, Chichkova V
Presse Med 2021 Nov;50(3):104075. Epub 2021 Sep 22 doi: 10.1016/j.lpm.2021.104075. PMID: 34562560

Diagnosis

Akinci G, Alyaarubi S, Patni N, Alhashmi N, Al-Shidhani A, Prodam F, Gagne N, Babalola F, Al Senani A, Muniraj K, Elsayed SM, Beghini M, Saydam BO, Allawati M, Vaishnav MS, Can E, Simsir IY, Sorkina E, Dursun F, Kamrath C, Cavdar U, Chakraborty PP, Dogan OA, Al Hosin A, Al Maimani A, Comunoglu N, Hamed A, Huseinbegovic T, Scherer T, Curtis J, Brown RJ, Topaloglu H, Simha V, Wabitsch M, Tuysuz B, Oral EA, Akinci B, Garg A
Am J Med Genet A 2024 Jun;194(6):e63533. Epub 2024 Jan 17 doi: 10.1002/ajmg.a.63533. PMID: 38234231Free PMC Article
Altarejos JY, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert AH, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim JH, Stevis P, Huang T, Zambrowicz B, Olson WC, Godin S, Bradley E, Gewitz AD, Baker M, Hench R, Davenport MS, Chenevert TL, DiPaola F, Yancopoulos GD, Murphy AJ, Herman GA, Musser BJ, Dansky H, Harp J, Gromada J, Sleeman MW, Oral EA, Olenchock BA
Sci Transl Med 2023 Nov 22;15(723):eadd4897. doi: 10.1126/scitranslmed.add4897. PMID: 37992152
Patni N, Garg A
Curr Diab Rep 2022 Sep;22(9):461-470. Epub 2022 Jul 11 doi: 10.1007/s11892-022-01485-w. PMID: 35821558Free PMC Article
Sorkina E, Chichkova V
Presse Med 2021 Nov;50(3):104075. Epub 2021 Sep 22 doi: 10.1016/j.lpm.2021.104075. PMID: 34562560
Garg A
Am J Med 2000 Feb;108(2):143-52. doi: 10.1016/s0002-9343(99)00414-3. PMID: 11126308

Therapy

Altarejos JY, Pangilinan J, Podgrabinska S, Akinci B, Foss-Freitas M, Neidert AH, Ray Y, Zheng W, Kim S, Kamat V, Huang M, Min S, Mastaitis J, Dominguez-Gutierrez G, Kim JH, Stevis P, Huang T, Zambrowicz B, Olson WC, Godin S, Bradley E, Gewitz AD, Baker M, Hench R, Davenport MS, Chenevert TL, DiPaola F, Yancopoulos GD, Murphy AJ, Herman GA, Musser BJ, Dansky H, Harp J, Gromada J, Sleeman MW, Oral EA, Olenchock BA
Sci Transl Med 2023 Nov 22;15(723):eadd4897. doi: 10.1126/scitranslmed.add4897. PMID: 37992152
Patni N, Garg A
Curr Diab Rep 2022 Sep;22(9):461-470. Epub 2022 Jul 11 doi: 10.1007/s11892-022-01485-w. PMID: 35821558Free PMC Article
Mainieri F, Tagi VM, Chiarelli F
Front Endocrinol (Lausanne) 2022;13:879979. Epub 2022 May 4 doi: 10.3389/fendo.2022.879979. PMID: 35600578Free PMC Article
Bande-Fernández JJ, García-Castro R, Sánchez-Alvarez JE, Rodríguez-Suárez C, Coronel-Aguilar D, Hidalgo C, Istanbuli B, Merino-Bueno C, Del Rio-García L
Nefrologia 2015;35(5):493-6. Epub 2015 Sep 19 doi: 10.1016/j.nefro.2015.08.002. PMID: 26391816
Tchang BG, Shukla AP, Aronne LJ
Expert Opin Biol Ther 2015 Jul;15(7):1061-75. doi: 10.1517/14712598.2015.1052789. PMID: 26063386

Prognosis

Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, Araújo-Vilar D
Front Endocrinol (Lausanne) 2023;14:1250203. Epub 2023 Nov 16 doi: 10.3389/fendo.2023.1250203. PMID: 38034001Free PMC Article
Su X, Lin Y, Liu L, Mei H, Xu A, Zeng C, Sheng H, Cheng J, Shao Y, Zheng R, Ting TH, Zhang W, Li X
J Pediatr Endocrinol Metab 2023 Jan 27;36(1):74-80. Epub 2022 Nov 28 doi: 10.1515/jpem-2022-0372. PMID: 36433712
Paauw ND, Stegeman R, de Vroede MAMJ, Termote JUM, Freund MW, Breur JMPJ
Eur J Pediatr 2020 Jan;179(1):39-50. Epub 2019 Dec 16 doi: 10.1007/s00431-019-03521-6. PMID: 31840185Free PMC Article
Hsu RH, Lin WD, Chao MC, Hsiao HP, Wong SL, Chiu PC, Chu SY, Ke YY, Lau BH, Chien YH, Hwu WL, Tsai FJ, Wang CH, Lee NC
J Formos Med Assoc 2019 Jan;118(1 Pt 1):142-147. Epub 2018 Mar 1 doi: 10.1016/j.jfma.2018.02.003. PMID: 29478747
Huang L, Shi H, Zhou X
Endocr Pract 2017 Jul;23(7):857-862. Epub 2017 Apr 27 doi: 10.4158/EP161686.RA. PMID: 28448764

Clinical prediction guides

Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, Araújo-Vilar D
Front Endocrinol (Lausanne) 2023;14:1250203. Epub 2023 Nov 16 doi: 10.3389/fendo.2023.1250203. PMID: 38034001Free PMC Article
Santos JL, Cortés VA
Obes Rev 2021 Jan;22(1):e13114. Epub 2020 Aug 2 doi: 10.1111/obr.13114. PMID: 33030294
Zou W, Rohatgi N, Brestoff JR, Zhang Y, Scheller EL, Craft CS, Brodt MD, Migotsky N, Silva MJ, Harris CA, Teitelbaum SL
PLoS Genet 2019 Jun;15(6):e1008244. Epub 2019 Jun 24 doi: 10.1371/journal.pgen.1008244. PMID: 31233501Free PMC Article
Broekema MF, Savage DB, Monajemi H, Kalkhoven E
Biochim Biophys Acta Mol Cell Biol Lipids 2019 May;1864(5):715-732. Epub 2019 Feb 8 doi: 10.1016/j.bbalip.2019.02.002. PMID: 30742913
Gupta N, Asi N, Farah W, Almasri J, Barrionuevo P, Alsawas M, Wang Z, Haymond MW, Brown RJ, Murad MH
J Clin Endocrinol Metab 2017 Feb 1;102(2):363-374. doi: 10.1210/jc.2016-2271. PMID: 27967300Free PMC Article

Recent systematic reviews

Gupta N, Asi N, Farah W, Almasri J, Barrionuevo P, Alsawas M, Wang Z, Haymond MW, Brown RJ, Murad MH
J Clin Endocrinol Metab 2017 Feb 1;102(2):363-374. doi: 10.1210/jc.2016-2271. PMID: 27967300Free PMC Article
Sivakumar T, Mechanic O, Fehmie DA, Paul B
HIV Med 2011 Sep;12(8):453-62. Epub 2011 Jan 25 doi: 10.1111/j.1468-1293.2010.00906.x. PMID: 21265979

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