MCID: ACQ022
MIFTS: 45

Acquired Generalized Lipodystrophy

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Immune diseases, Metabolic diseases, Muscle diseases, Rare diseases, Skin diseases

Aliases & Classifications for Acquired Generalized Lipodystrophy

MalaCards integrated aliases for Acquired Generalized Lipodystrophy:

Name: Acquired Generalized Lipodystrophy 12 20 58 36 54 15
Lawrence Syndrome 12 20 58
Acquired Lipoatrophic Diabetes 20 58
Lawrence-Seip Syndrome 20 58
Familial Generalized Lipodystrophy 71

Characteristics:

Orphanet epidemiological data:

58
acquired generalized lipodystrophy
Inheritance: Not applicable; Prevalence: 1-9/100000 (Europe); Age of onset: All ages;

Classifications:

Orphanet: 58  
Rare skin diseases
Rare endocrine diseases


Summaries for Acquired Generalized Lipodystrophy

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79086DefinitionA rare lipodystrophic syndrome characterized by loss of adipose tissue, and is a syndrome of insulin resistance that leads to increased cardiovascular risk. Acquired generalized lipodystrophy is related to a selective loss of subcutaneous adipose tissue occurring exclusively at the extremities (face, legs, arms, palms and sometimes soles).EpidemiologyMore than 100 cases have been described and the female to male ratio is 3:1.Clinical descriptionThe clinical phenotype is similar to that of Berardinelli-Seip syndrome (see this term), but lipoatrophy appears secondarily during childhood, adolescence or adulthood, and as a result the syndrome is thought to be acquired. In some cases, loss of adipose tissue is localized, especially if it is preceded by a panniculitis. The syndrome is associated with a voracious appetite and an acceleration of growth in adolescents. One third of cases are accompanied by acanthosis nigricans and a polycystic ovary syndrome (see these terms). Hepatomegaly with steatosis and a risk of cirrhogenous progression is common. Biologically, hyperinsulinemia and insulin-resistant diabetes are observed, often associated with severe hypertriglyceridemia with low plasma levels of leptin and adiponectin. Proteinuria associated with focal segmental glomerulosclerosis or with membranoproliferative glomerulonephritis have been reported recently, as well as dysregulation of growth hormone. Three types of the disease have been described: 1) a form with panniculitis (inflammatory nodules followed by lipoatrophy), 2) an autoimmune form that is readily associated with other syndromes such as chronic active hepatitis, Hashimoto struma and hemolytic anemia, but also with dermatomyositis and Sjogren's syndrome (see these terms), 3) idiopathic.EtiologyThe cause of the disease remains unknown. There may be infectious triggering factors (there was a recent case of the panniculitis type that appeared after tuberculosis) or an autoimmune mechanism. A recent publication showed activation of the classical complement pathway (low C4). This is in contrast to acquired partial lipodystrophy (see this term) which affects the upper half of the body and is characterized by an activation of the alternative complement pathway (low C3). Progression towards partial lipoatrophy, focal or generalized, has been reported in patients with dermatomyositis, amongst whom this could be a late relapse, and it is more common that the antibody anti-p155 is present. The hypothesis of an underlying genetic factor has not been rejected.Diagnostic methodsDiagnosis is clinical and should be confirmed by an assessment of body fat, in particular by biphotonic absorptiometry and magnetic resonance imaging.Differential diagnosisDifferential diagnoses include other forms of extreme insulin resistance (Rabson-Mendenhall syndrome, leprechaunism, Berardinelli type lipodystrophy and insulin resistance syndromes types A and B; see these terms) and other lipodystrophies.Management and treatmentThe treatment of the metabolic manifestations is a priori no different to the treatment of other forms of insulin resistance: physical exercise, insulin sensitizers such as metformin or pioglitazone, insulin (or preferably insulin analogues), antihypertensives, and monitoring and treatment of hypertriglyceridemia. The efficacy of recombinant human leptin has been demonstrated on the metabolic level but this therapy is not available in all countries. In serious autoimmune forms of the disease, immunosuppressive therapy may be indicated.PrognosisThe prognosis is not well known but is probably related to cardiovascular risk (linked to the insulin-resistance syndrome) and to the underlying cause of the disease.Visit the Orphanet disease page for more resources.

MalaCards based summary : Acquired Generalized Lipodystrophy, also known as lawrence syndrome, is related to hyperinsulinism and hyperglycemia. An important gene associated with Acquired Generalized Lipodystrophy is ADIPOQ (Adiponectin, C1Q And Collagen Domain Containing), and among its related pathways/superpathways are Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha) and Glucose / Energy Metabolism. Affiliated tissues include bone marrow, ovary and bone, and related phenotypes are generalized lipodystrophy and hyperinsulinemia

Disease Ontology : 12 A complete generalized lipodystrophy that is charcterized by generalized disappearance of fat occurring during childhood and adolescence where normal body fat is present at birth.

KEGG : 36 Acquired generalized lipodystrophy (AGL), also called the Lawrence syndrome, is one subtype of acquired lipodystrophy caused by autoimmune disease, panniculitis or idiopathic. The disorder appears during the childhood and adolescence. Clinically, loss of subcutaneous fat occurs highly variable, exclusively at the face and extremities including legs, palms and some soles. In rare cases, intraabdomianl fat and bone marrow fat may also be spared. Similarly to congential generalized lipodystrophy, people with the disorder usually appear severe hepatic steatosis and fibrosis, diabetes, and hypertriglyceridemia. Metreleptin, as a recombinant analog of human leptin, has been approved for the treatment for the disorder as well as diet.

Wikipedia : 74 Acquired generalized lipodystrophy (also known as "Lawrence syndrome," and "Lawrence-Seip syndrome",... more...

Related Diseases for Acquired Generalized Lipodystrophy

Diseases in the Acquired Generalized Lipodystrophy family:

Lipodystrophy, Congenital Generalized, Type 2 Lipodystrophy, Congenital Generalized, Type 1
Lipodystrophy, Congenital Generalized, Type 3 Lipodystrophy, Congenital Generalized, Type 4
Congenital Generalized Lipodystrophy

Diseases related to Acquired Generalized Lipodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 121)
# Related Disease Score Top Affiliating Genes
1 hyperinsulinism 30.4 RETN LEP ADIPOQ
2 hyperglycemia 30.3 RETN LEP ADIPOQ
3 acanthosis nigricans 30.3 LMNA LEP ADIPOQ
4 fatty liver disease 30.2 RETN LEP ADIPOQ
5 berardinelli-seip congenital lipodystrophy 30.0 LEP BSCL2 AGPAT2
6 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 30.0 ZMPSTE24 LMNA LEP BSCL2 AGPAT2 ADIPOQ
7 lipid metabolism disorder 29.9 RETN LMNA LEP ADIPOQ
8 umbilical hernia 29.9 BSCL2 AGPAT2
9 hypothyroidism 29.6 RETN LEP ADIPOQ
10 type 1 diabetes mellitus 29.5 RETN LEP ADIPOQ
11 type 2 diabetes mellitus 28.7 RETN PLIN1 LMNA LEP BSCL2 AGPAT2
12 diabetes mellitus 28.7 RETN PLIN1 LMNA LEP BSCL2 ADIPOQ
13 congenital generalized lipodystrophy 27.6 ZMPSTE24 PLIN1 LMNA LEP CIDEC CAVIN1
14 hypertriglyceridemia, familial 10.5
15 fatty liver disease, nonalcoholic 1 10.3
16 non-alcoholic fatty liver disease 10.3
17 panniculitis 10.3
18 nontuberculous mycobacterial lung disease 10.2 LEP ADIPOQ
19 hypothalamic obesity 10.2 RETN LEP
20 abdominal obesity-metabolic syndrome quantitative trait locus 2 10.2 LEP ADIPOQ
21 alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity 10.2
22 adult syndrome 10.1 LEP ADIPOQ
23 autoimmune disease 10.1
24 peripheral t-cell lymphoma 10.1
25 lymphoma 10.1
26 non-alcoholic steatohepatitis 10.1
27 autoimmune hepatitis 10.1
28 hemolytic anemia 10.1
29 acquired lipodystrophy 10.1
30 donohue syndrome 10.1 BSCL2 AGPAT2
31 muscle hypertrophy 10.1
32 intracranial hypertension 10.1 RETN ADIPOQ
33 idiopathic recurrent pericarditis 10.1 RETN LEP ADIPOQ
34 pericarditis 10.1 RETN LEP ADIPOQ
35 obesity-hypoventilation syndrome 10.1 RETN LEP ADIPOQ
36 maturity-onset diabetes of the young, type 1 10.1 RETN LEP ADIPOQ
37 apnea, obstructive sleep 10.1 RETN LEP ADIPOQ
38 nutritional deficiency disease 10.1 RETN LEP ADIPOQ
39 prediabetes syndrome 10.1 RETN LEP ADIPOQ
40 sleep apnea 10.1 RETN LEP ADIPOQ
41 abdominal obesity-metabolic syndrome 1 10.1 RETN LEP ADIPOQ
42 gestational diabetes 10.1 RETN LEP ADIPOQ
43 inherited metabolic disorder 10.1 RETN LEP ADIPOQ
44 anorexia nervosa 10.1 RETN LEP ADIPOQ
45 polycystic ovary syndrome 10.1 RETN LEP ADIPOQ
46 atherosclerosis susceptibility 10.0 RETN LEP ADIPOQ
47 glucose metabolism disease 10.0 RETN LEP ADIPOQ
48 acquired metabolic disease 10.0 RETN LEP ADIPOQ
49 monogenic diabetes 10.0 LMNA BSCL2
50 mandibuloacral dysplasia with type a lipodystrophy 10.0 ZMPSTE24 LMNA

Graphical network of the top 20 diseases related to Acquired Generalized Lipodystrophy:



Diseases related to Acquired Generalized Lipodystrophy

Symptoms & Phenotypes for Acquired Generalized Lipodystrophy

Human phenotypes related to Acquired Generalized Lipodystrophy:

58 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 generalized lipodystrophy 58 31 obligate (100%) Obligate (100%) HP:0009064
2 hyperinsulinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000842
3 hepatic steatosis 58 31 frequent (33%) Frequent (79-30%) HP:0001397
4 autoimmunity 58 31 frequent (33%) Frequent (79-30%) HP:0002960
5 cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001638
6 progeroid facial appearance 58 31 frequent (33%) Frequent (79-30%) HP:0005328
7 insulin-resistant diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000831
8 calf muscle pseudohypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003707
9 hypertension 58 31 occasional (7.5%) Occasional (29-5%) HP:0000822
10 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
11 proteinuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0000093
12 myopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003198
13 hypertriglyceridemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002155
14 cirrhosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001394
15 polycystic ovaries 58 31 occasional (7.5%) Occasional (29-5%) HP:0000147
16 generalized hirsutism 58 31 occasional (7.5%) Occasional (29-5%) HP:0002230
17 generalized hyperpigmentation 58 31 occasional (7.5%) Occasional (29-5%) HP:0007440
18 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
19 accelerated skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0005616
20 panniculitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0012490
21 abnormality of complement system 58 31 occasional (7.5%) Occasional (29-5%) HP:0005339
22 acute pancreatitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001735
23 lymphoma 58 31 very rare (1%) Very rare (<4-1%) HP:0002665
24 astrocytoma 58 31 very rare (1%) Very rare (<4-1%) HP:0009592
25 unicameral bone cyst 58 31 very rare (1%) Very rare (<4-1%) HP:0012064
26 abnormality of lipid metabolism 58 Frequent (79-30%)
27 abnormality of cardiovascular system physiology 58 Frequent (79-30%)
28 insulin resistance 58 Very frequent (99-80%)

MGI Mouse Phenotypes related to Acquired Generalized Lipodystrophy:

46 (show all 14)
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 10.19 ADIPOQ AGPAT2 BSCL2 CIDEC LEP LMNA
2 behavior/neurological MP:0005386 10.18 ADIPOQ AGPAT2 BSCL2 CAVIN1 CIDEC LEP
3 growth/size/body region MP:0005378 10.11 ADIPOQ AGPAT2 BSCL2 CAVIN1 CIDEC LEP
4 homeostasis/metabolism MP:0005376 10.1 ADIPOQ AGPAT2 BSCL2 CAVIN1 CIDEC LEP
5 cellular MP:0005384 10.05 ADIPOQ AGPAT2 BSCL2 CAVIN1 LEP LMNA
6 hematopoietic system MP:0005397 9.98 ADIPOQ AGPAT2 BSCL2 CIDEC LEP LMNA
7 endocrine/exocrine gland MP:0005379 9.95 ADIPOQ AGPAT2 BSCL2 LEP LMNA ZMPSTE24
8 integument MP:0010771 9.92 ADIPOQ AGPAT2 BSCL2 CIDEC LEP LMNA
9 immune system MP:0005387 9.91 ADIPOQ AGPAT2 BSCL2 LEP LMNA RETN
10 digestive/alimentary MP:0005381 9.89 AGPAT2 BSCL2 LEP LMNA ZMPSTE24
11 liver/biliary system MP:0005370 9.81 ADIPOQ AGPAT2 BSCL2 CIDEC LEP LMNA
12 limbs/digits/tail MP:0005371 9.65 AGPAT2 BSCL2 LEP LMNA ZMPSTE24
13 muscle MP:0005369 9.43 ADIPOQ CAVIN1 LEP LMNA PLIN1 ZMPSTE24
14 renal/urinary system MP:0005367 9.17 ADIPOQ AGPAT2 BSCL2 CAVIN1 LEP LMNA

Drugs & Therapeutics for Acquired Generalized Lipodystrophy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Compassionate Use of Metreleptin in Previously-Treated Patients With Partial Lipodystrophy Recruiting NCT02262806 Phase 3 Metreleptin

Search NIH Clinical Center for Acquired Generalized Lipodystrophy

Genetic Tests for Acquired Generalized Lipodystrophy

Anatomical Context for Acquired Generalized Lipodystrophy

MalaCards organs/tissues related to Acquired Generalized Lipodystrophy:

40
Bone Marrow, Ovary, Bone, Liver, Adipocyte

Publications for Acquired Generalized Lipodystrophy

Articles related to Acquired Generalized Lipodystrophy:

(show top 50) (show all 67)
# Title Authors PMID Year
1
Leptin therapy for partial lipodystrophy linked to a PPAR-gamma mutation. 61 54
18076675 2008
2
Lipoatrophic diabetes in an elderly woman: clinical course and serum adipocytokine concentrations. 61 54
15256772 2004
3
Effect of leptin replacement on intrahepatic and intramyocellular lipid content in patients with generalized lipodystrophy. 61 54
12502655 2003
4
Serum adiponectin and leptin levels in patients with lipodystrophies. 61 54
11994394 2002
5
Acquired generalized lipodystrophy under immune checkpoint inhibition. 61
31077337 2020
6
Imaging spectrum of abnormal subcutaneous and visceral fat distribution. 61
32056035 2020
7
A CASE OF ACQUIRED GENERALIZED LIPODYSTROPHY ASSOCIATED WITH PEMBROLIZUMAB IN A PATIENT WITH METASTATIC MALIGNANT MELANOMA. 61
32524008 2020
8
Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy. 61
32010873 2020
9
Leptin induces TNF╬▒-dependent inflammation in acquired generalized lipodystrophy and combined Crohn's disease. 61
31822667 2019
10
Surgical fat removal exacerbates metabolic disorders but not atherogenesis in LDLR-/- mice fed on high-fat diet. 61
31780791 2019
11
Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes. 61
31434650 2019
12
Acquired Lipodystrophy Associated With Nivolumab in a Patient With Advanced Renal Cell Carcinoma. 61
30779841 2019
13
Fatty Liver and Autoimmune Hepatitis: Two Forms of Liver Involvement in Lipodystrophies. 61
31559327 2019
14
An overview of lipodystrophy and the role of the complement system. 61
31177059 2019
15
Diagnosis and treatment of lipodystrophy: a step-by-step approach. 61
29704234 2019
16
Diagnosis of acquired generalized lipodystrophy in a single patient with T-cell lymphoma and no exposure to Metreleptin. 61
30923630 2019
17
Case Report of Acquired Generalized Lipodystrophy Associated With Common Variable Immunodeficiency. 61
29846625 2018
18
Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. 61
29644599 2018
19
Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis. 61
29610677 2018
20
Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy. 61
30283460 2018
21
Determining residual adipose tissue characteristics with MRI in patients with various subtypes of lipodystrophy. 61
29044029 2017
22
Acquired Generalized Lipodystrophy Following Immune Thrombocytopenia. 61
28549922 2017
23
Clinical Features and Management of Non-HIV-Related Lipodystrophy in Children: A Systematic Review. 61
27967300 2017
24
Lipodystrophy Syndromes. 61
27823605 2016
25
Bone imaging findings in genetic and acquired lipodystrophic syndromes: an imaging study of 24 cases. 61
27631079 2016
26
Cover Image: Acquired generalized lipodystrophy in a patient with systemic lupus erythematosus. 61
27484277 2016
27
Lymphoma in acquired generalized lipodystrophy. 61
25864863 2016
28
Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. 61
26465174 2016
29
Acquired generalized lipodystrophy in a young lean Chinese girl. Case Report. 61
26859586 2015
30
A Report of Three Cases With Acquired Generalized Lipodystrophy With Distinct Autoimmune Conditions Treated With Metreleptin. 61
26390101 2015
31
A Novel Syndrome of Generalized Lipodystrophy Associated With Pilocytic Astrocytoma. 61
26252356 2015
32
Acquired generalized lipodystrophy associated with peripheral T cell lymphoma with cutaneous infiltration. 61
24168394 2015
33
Leptin in congenital and HIV-associated lipodystrophy. 61
25267014 2015
34
Exploring the pathophysiology behind the more common genetic and acquired lipodystrophies. 61
24152769 2014
35
Post-liver transplant leptin results in resolution of severe recurrence of lipodystrophy-associated nonalcoholic steatohepatitis. 61
24007548 2013
36
Response to comments on "Late-onset acquired generalized lipodystrophy with muscle involvement". 61
23962584 2013
37
Comment on: late-onset acquired generalized lipodystrophy with muscle involvement. 61
23985087 2013
38
The liver diseases of lipodystrophy: the long-term effect of leptin treatment. 61
23439261 2013
39
Late-onset acquired generalized lipodystrophy with muscle involvement. 61
22188950 2012
40
Consequences of stopping and restarting leptin in an adolescent with lipodystrophy. 61
22965160 2012
41
Cardiomyopathy in congenital and acquired generalized lipodystrophy: a clinical assessment. 61
20616664 2010
42
Case report: unicameral bone cysts in a young patient with acquired generalized lipodystrophy. 61
19924491 2010
43
Acquired generalized lipodystrophy associated with autoimmune hepatitis and low serum C4 level. 61
21274335 2010
44
Complement abnormalities in acquired lipodystrophy revisited. 61
18854390 2009
45
Type 1 diabetes associated with acquired generalized lipodystrophy and insulin resistance: the effect of long-term leptin therapy. 61
17940115 2008
46
[Acquired generalized lipodystrophy. Literature review and own observation]. 61
19145855 2008
47
Acquired generalized lipodystrophy (panniculitis variety) triggered by pulmonary tuberculosis. 61
17651183 2007
48
[Primary lipodystrophies]. 61
17320032 2007
49
Dysregulation of growth hormone in acquired generalized lipodystrophy. 61
15573230 2004
50
A case of acquired generalized lipodystrophy with cerebellar degeneration and type 2 diabetes mellitus. 61
17491704 2004

Variations for Acquired Generalized Lipodystrophy

Expression for Acquired Generalized Lipodystrophy

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

Pathways for Acquired Generalized Lipodystrophy

GO Terms for Acquired Generalized Lipodystrophy

Cellular components related to Acquired Generalized Lipodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.17 ZMPSTE24 PLIN1 CIDEC CAVIN1 BSCL2 AGPAT2
2 lipid droplet GO:0005811 9.13 PLIN1 CIDEC BSCL2

Biological processes related to Acquired Generalized Lipodystrophy according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.71 PLIN1 LEP BSCL2 AGPAT2
2 positive regulation of cytokine production GO:0001819 9.49 LEP AGPAT2
3 response to activity GO:0014823 9.48 LEP ADIPOQ
4 fatty acid beta-oxidation GO:0006635 9.46 LEP ADIPOQ
5 nucleus organization GO:0006997 9.43 ZMPSTE24 LMNA
6 regulation of glucose metabolic process GO:0010906 9.37 ZMPSTE24 ADIPOQ
7 lipid droplet organization GO:0034389 9.32 CIDEC BSCL2
8 nuclear envelope organization GO:0006998 9.26 ZMPSTE24 LMNA
9 determination of adult lifespan GO:0008340 9.16 ZMPSTE24 LEP
10 positive regulation of cold-induced thermogenesis GO:0120162 9.13 LEP BSCL2 ADIPOQ
11 regulation of protein localization to nucleus GO:1900180 8.62 LMNA LEP

Molecular functions related to Acquired Generalized Lipodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.8 RETN LEP ADIPOQ

Sources for Acquired Generalized Lipodystrophy

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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30 HMDB
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
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44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
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54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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