MCID: LPD015
MIFTS: 51

Lipodystrophy, Familial Partial, Type 2

Categories: Genetic diseases, Rare diseases, Skin diseases, Endocrine diseases, Fetal diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Lipodystrophy, Familial Partial, Type 2

MalaCards integrated aliases for Lipodystrophy, Familial Partial, Type 2:

Name: Lipodystrophy, Familial Partial, Type 2 54 50
Lipoatrophic Diabetes 12 50 71 14
Fpld2 50 24 56 71
Familial Partial Lipodystrophy, Dunnigan Type 50 24 56
Familial Partial Lipodystrophy Type 2 50 24 56
Lipodystrophy, Familial Partial, 2 71 13
Dunnigan Syndrome 50 56
Fpl2 50 71
Generalized Lipoatrophy Associated with Diabetes, Hepatic Steatosis, Hypertrophic Cardiomyopathy and Leukomelanodermic Papules 71
Lipodystrophy, Familial, of Limbs and Lower Trunk 50
Lipodystrophy Familial of Limbs and Lower Trunk 71
Lipodystrophy, Familial Partial, Dunnigan Type 50
Familial Partial Lipodystrophy Dunnigan Type 71
Familial Partial Lipodystrophy, Type 2 69
Familial Generalized Lipodystrophy 69
Familial Partial Lipodystrophy 2 29
Diabetes Mellitus, Lipoatrophic 42
Lipodystrophy, Reverse Partial 50
Lipoatrophic Diabetes Mellitus 69
Lipodystrophy Reverse Partial 71

Characteristics:

Orphanet epidemiological data:

56
familial partial lipodystrophy, dunnigan type
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult; Age of death: adult,elderly;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
onset of clinical features around puberty


HPO:

32
lipodystrophy, familial partial, type 2:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Lipodystrophy, Familial Partial, Type 2

OMIM : 54
Familial partial lipodystrophy is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently. Familial partial lipodystrophy may also be referred to as lipoatrophic diabetes mellitus, but the essential feature is loss of subcutaneous fat (review by Garg, 2004). The disorder may be misdiagnosed as Cushing disease (see 219080) (Kobberling and Dunnigan, 1986; Garg, 2004). (151660)

MalaCards based summary : Lipodystrophy, Familial Partial, Type 2, also known as lipoatrophic diabetes, is related to aredyld and lipodystrophy, congenital generalized, type 2, and has symptoms including hypertriglyceridemia, hepatomegaly and splenomegaly. An important gene associated with Lipodystrophy, Familial Partial, Type 2 is LMNA (Lamin A/C), and among its related pathways/superpathways are Regulation of lipid metabolism Insulin signaling-generic cascades and Vascular smooth muscle contraction. Affiliated tissues include liver, skin and skeletal muscle, and related phenotypes are adipose tissue and pigmentation

NIH Rare Diseases : 50 familial partial lipodystrophy type 2 is a rare genetic condition that affects the amount and distribution of fat in the body. it is characterized by a loss of fatty tissue from the torso, buttocks, and limbs and a buildup of fat in the face, neck, shoulders and abdomen. symptoms typically develop around puberty. this condition can be associated with a number of metabolic complications, including insulin resistance, high blood cholesterol levels (dyslipidemia), diabetes, and liver steatosis. these metabolic complications lead to an increased risk for cardiovascular disease. familial partial lipodystrophy type 2 is caused by mutations in the lmna gene. it is inherited in an autosomal dominant manner. treatment includes correction of metabolic abnormalities and management of complications through diet, exercise, and medications.    last updated: 7/3/2016

UniProtKB/Swiss-Prot : 71 Lipodystrophy, familial partial, 2: A disorder characterized by the loss of subcutaneous adipose tissue in the lower parts of the body (limbs, buttocks, trunk). It is accompanied by an accumulation of adipose tissue in the face and neck causing a double chin, fat neck, or cushingoid appearance. Adipose tissue may also accumulate in the axillae, back, labia majora, and intraabdominal region. Affected patients are insulin-resistant and may develop glucose intolerance and diabetes mellitus after age 20 years, hypertriglyceridemia, and low levels of high density lipoprotein cholesterol.

Disease Ontology : 12 A type 2 diabetes that involves severe lipodystrophy in addition to the traditional signs of diabetes.

Related Diseases for Lipodystrophy, Familial Partial, Type 2

Diseases in the Familial Partial Lipodystrophy family:

Lipodystrophy, Familial Partial, Type 2 Lipodystrophy, Familial Partial, Type 5
Lipodystrophy, Familial Partial, Type 3 Lipodystrophy, Familial Partial, Type 4
Lipodystrophy, Partial, Acquired Lipodystrophy, Familial Partial, Type 6
Lipodystrophy, Familial Partial, Type 1 Familial Partial Lipodystrophy Due to Akt2 Mutations
Lipe-Related Familial Partial Lipodystrophy

Diseases related to Lipodystrophy, Familial Partial, Type 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 52)
id Related Disease Score Top Affiliating Genes
1 aredyld 11.8
2 lipodystrophy, congenital generalized, type 2 11.2
3 lipodystrophy, familial partial, type 1 11.2
4 acquired generalized lipodystrophy 11.1
5 lipodystrophy, congenital generalized, type 1 11.0
6 inflammatory bowel disease 10.3 LEP LMNA
7 myh-9 related disease 10.3 INS LEP
8 hypomagnesemia 3, renal 10.3 INS LEP
9 fetal parvovirus syndrome 10.3 INS LEP
10 hyperlipoproteinemia type iv 10.3 INS LEP
11 neurogenic arthropathy 10.2 INS LEP
12 alstrom syndrome 10.2 INS LEP
13 nonsyndromic hereditary sensorineural hearing loss 10.2 INS LEP
14 chondroma 10.2 INS LEP
15 porokeratosis 10.2 INS LEP
16 hyperchylomicronemia, late-onset 10.2 INS LMNA
17 diabetic encephalopathy 10.2 INS LEP
18 periampullary adenoma 10.2 INS LEP
19 inherited metabolic disorder 10.2 INS LEP
20 intramuscular hemangioma 10.2 INS LEP
21 skin squamous cell carcinoma 10.2 INS LEP
22 hypertrichosis 10.2 INS LEP
23 mucolipidoses 10.2 INS LEP
24 lipodystrophy 10.1
25 survival motor neuron spinal muscular atrophy 10.1 INS LEP
26 familial partial lipodystrophy 10.1
27 skin meningioma 10.1 INS LEP
28 lung cancer susceptibility 2 10.1 INS LEP
29 antidepressant type abuse 10.1 INS LEP
30 exostosis 10.0 INS LEP
31 dientamoebiasis 9.9 INS LEP
32 chronic myelomonocytic leukemia 9.9 INS LEP
33 congenital generalized lipodystrophy 9.9
34 hyperglycemia 9.9
35 lissencephaly 9.9 INS LEP LMNA
36 mucinoses 9.9 INS LEP LMNA
37 short bowel syndrome 9.9 INS LEP LMNA
38 mature gastric teratoma 9.9 INS LEP LMNA
39 precursor b lymphoblastic lymphoma/leukemia 9.8 INS LEP
40 retinal degeneration 9.7
41 neuropathy 9.7
42 hypertriglyceridemia 9.7
43 nonalcoholic steatohepatitis 9.7
44 ectodermal dysplasia 9.7
45 hepatitis 9.7
46 liver disease 9.7
47 dermatomyositis 9.7
48 rickets 9.7
49 retinitis 9.7
50 pancreatitis 9.7

Graphical network of the top 20 diseases related to Lipodystrophy, Familial Partial, Type 2:



Diseases related to Lipodystrophy, Familial Partial, Type 2

Symptoms & Phenotypes for Lipodystrophy, Familial Partial, Type 2

Symptoms via clinical synopsis from OMIM:

54

Abdomen- Liver:
hepatomegaly
hepatic steatosis

Cardiovascular- Vascular:
hypertension
prominent superficial veins
atherosclerosis

Head And Neck- Face:
normal or increased facial adipose tissue
round, full face

Skin Nails & Hair- Skin:
prominent superficial veins
xanthomata
acanthosis nigricans (uncommon)

Genitourinary- External Genitalia Female:
labial pseudohypertrophy
polycystic ovary disease (uncommon)

Neurologic- Peripheral Nervous System:
nerve compression
nerve entrapment syndromes
enlarged peripheral nerves
tomaculae (paranodal myelin swellings)

Laboratory- Abnormalities:
hyperglycemia
hyperinsulinemia
increased serum triglycerides
decreased hdl cholesterol

Muscle Soft Tissue:
myalgia
partial lipodystrophy (abnormal distribution of subcutaneous adipose tissue)
loss of subcutaneous truncal adipose tissue
loss of subcutaneous adipose tissue in limbs
loss of adipose tissue occurs around puberty
more
Head And Neck- Neck:
normal or increased adipose tissue around the neck

Abdomen- Pancreas:
pancreatitis, acute in some

Skin Nails & Hair- Hair:
hirsutism (uncommon)

Endocrine Features:
insulin-resistant diabetes mellitus (onset around puberty)


Clinical features from OMIM:

151660

Human phenotypes related to Lipodystrophy, Familial Partial, Type 2:

56 32 (show top 50) (show all 51)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertriglyceridemia 56 32 hallmark (90%) Very frequent (99-80%) HP:0002155
2 hepatomegaly 56 32 hallmark (90%) Very frequent (99-80%) HP:0002240
3 splenomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001744
4 secondary amenorrhea 56 32 frequent (33%) Frequent (79-30%) HP:0000869
5 round face 56 32 hallmark (90%) Very frequent (99-80%) HP:0000311
6 hypertrophic cardiomyopathy 56 32 occasional (7.5%) Occasional (29-5%) HP:0001639
7 thin skin 56 32 frequent (33%) Frequent (79-30%) HP:0000963
8 pancreatitis 56 32 occasional (7.5%) Occasional (29-5%) HP:0001733
9 myopathy 56 32 occasional (7.5%) Occasional (29-5%) HP:0003198
10 myalgia 56 32 occasional (7.5%) Occasional (29-5%) HP:0003326
11 congestive heart failure 56 32 occasional (7.5%) Occasional (29-5%) HP:0001635
12 atherosclerosis 56 32 Frequent (79-30%) HP:0002621
13 hepatic steatosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0001397
14 loss of subcutaneous adipose tissue in limbs 56 32 frequent (33%) Frequent (79-30%) HP:0003635
15 diabetes mellitus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000819
16 cellulitis 56 32 occasional (7.5%) Occasional (29-5%) HP:0100658
17 lipodystrophy 56 32 Very frequent (99-80%) HP:0009125
18 coronary artery disease 56 32 occasional (7.5%) Occasional (29-5%) HP:0001677
19 acanthosis nigricans 56 32 occasional (7.5%) Occasional (29-5%) HP:0000956
20 insulin resistance 56 32 hallmark (90%) Very frequent (99-80%) HP:0000855
21 polycystic ovaries 56 32 occasional (7.5%) Occasional (29-5%) HP:0000147
22 lipoatrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0100578
23 cranial nerve paralysis 56 32 occasional (7.5%) Occasional (29-5%) HP:0006824
24 generalized hirsutism 56 32 occasional (7.5%) Occasional (29-5%) HP:0002230
25 abnormality of the nail 56 32 frequent (33%) Frequent (79-30%) HP:0001597
26 glomerulopathy 56 32 occasional (7.5%) Occasional (29-5%) HP:0100820
27 skeletal muscle hypertrophy 56 32 hallmark (90%) Very frequent (99-80%) HP:0003712
28 advanced eruption of teeth 56 32 frequent (33%) Frequent (79-30%) HP:0006288
29 dysmenorrhea 56 32 occasional (7.5%) Occasional (29-5%) HP:0100607
30 xanthomatosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0000991
31 abnormality of complement system 56 32 occasional (7.5%) Occasional (29-5%) HP:0005339
32 abnormality of skeletal muscle fiber size 56 32 occasional (7.5%) Occasional (29-5%) HP:0012084
33 eclampsia 56 32 occasional (7.5%) Occasional (29-5%) HP:0100601
34 hirsutism 32 HP:0001007
35 insulin-resistant diabetes mellitus 32 HP:0000831
36 hyperglycemia 32 HP:0003074
37 hyperinsulinemia 32 HP:0000842
38 hypertension 32 HP:0000822
39 prominent superficial veins 32 HP:0001015
40 labial pseudohypertrophy 32 HP:0008739
41 increased intramuscular fat 32 HP:0008985
42 increased intraabdominal fat 32 HP:0008993
43 hypoalphalipoproteinemia 32 HP:0003233
44 aplasia/hypoplasia of the skin 56 Very frequent (99-80%)
45 reduced subcutaneous adipose tissue 32 HP:0003758
46 acute pancreatitis 32 frequent (33%) HP:0001735
47 increased adipose tissue around the neck 32 HP:0000468
48 increased facial adipose tissue 32 HP:0000287
49 adipose tissue loss 32 HP:0008887
50 loss of truncal subcutaneous adipose tissue 32 HP:0009002

UMLS symptoms related to Lipodystrophy, Familial Partial, Type 2:


myalgia

MGI Mouse Phenotypes related to Lipodystrophy, Familial Partial, Type 2:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 9.55 GFPT2 INS LEP LMNA PDE3B
2 pigmentation MP:0001186 9.13 LEP LMNA PDE3B
3 vision/eye MP:0005391 8.92 GFPT2 INS LEP LMNA

Drugs & Therapeutics for Lipodystrophy, Familial Partial, Type 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Leptin to Treat Lipodystrophy Completed NCT00025883 Phase 2 Metreleptin

Search NIH Clinical Center for Lipodystrophy, Familial Partial, Type 2

Cochrane evidence based reviews: diabetes mellitus, lipoatrophic

Genetic Tests for Lipodystrophy, Familial Partial, Type 2

Genetic tests related to Lipodystrophy, Familial Partial, Type 2:

id Genetic test Affiliating Genes
1 Familial Partial Lipodystrophy 2 29
2 Familial Partial Lipodystrophy Type 2 24 LMNA

Anatomical Context for Lipodystrophy, Familial Partial, Type 2

MalaCards organs/tissues related to Lipodystrophy, Familial Partial, Type 2:

39
Liver, Skin, Skeletal Muscle, Ovary, Heart

Publications for Lipodystrophy, Familial Partial, Type 2

Variations for Lipodystrophy, Familial Partial, Type 2

UniProtKB/Swiss-Prot genetic disease variations for Lipodystrophy, Familial Partial, Type 2:

71 (show all 16)
id Symbol AA change Variation ID SNP ID
1 LMNA p.Gly465Asp VAR_009989 rs61282106
2 LMNA p.Arg482Leu VAR_009991 rs11575937
3 LMNA p.Arg482Gln VAR_009992 rs11575937
4 LMNA p.Arg482Trp VAR_009993 rs57920071
5 LMNA p.Lys486Asn VAR_009994 rs59981161
6 LMNA p.Arg527Pro VAR_009995 rs57520892
7 LMNA p.Arg582His VAR_009998 rs57830985
8 LMNA p.Arg133Leu VAR_016913 rs60864230
9 LMNA p.Arg60Gly VAR_034706 rs28928900
10 LMNA p.Arg28Trp VAR_039748 rs59914820
11 LMNA p.Arg62Gly VAR_039755 rs56793579
12 LMNA p.Asp230Asn VAR_039770 rs61214927
13 LMNA p.Arg399Cys VAR_039778 rs58672172
14 LMNA p.Ser573Leu VAR_039789 rs60890628
15 LMNA p.Arg439Cys VAR_070181 rs62636506
16 LMNA p.Lys515Glu VAR_071968

ClinVar genetic disease variations for Lipodystrophy, Familial Partial, Type 2:

6 (show all 17)
id Gene Variation Type Significance SNP ID Assembly Location
1 LMNA NM_170707.3(LMNA): c.178C> G (p.Arg60Gly) single nucleotide variant Pathogenic rs28928900 GRCh37 Chromosome 1, 156084887: 156084887
2 LMNA NM_170707.3(LMNA): c.1580G> C (p.Arg527Pro) single nucleotide variant Pathogenic rs57520892 GRCh37 Chromosome 1, 156106995: 156106995
3 LMNA NM_170707.3(LMNA): c.1445G> A (p.Arg482Gln) single nucleotide variant Pathogenic rs11575937 GRCh37 Chromosome 1, 156106776: 156106776
4 LMNA NM_170707.3(LMNA): c.398G> T (p.Arg133Leu) single nucleotide variant Pathogenic rs60864230 GRCh37 Chromosome 1, 156100449: 156100449
5 LMNA NM_005572.3(LMNA): c.1444C> T (p.Arg482Trp) single nucleotide variant Pathogenic rs57920071 GRCh37 Chromosome 1, 156106775: 156106775
6 LMNA NM_170707.3(LMNA): c.1445G> T (p.Arg482Leu) single nucleotide variant Pathogenic rs11575937 GRCh37 Chromosome 1, 156106776: 156106776
7 LMNA NM_170707.3(LMNA): c.1394G> A (p.Gly465Asp) single nucleotide variant Pathogenic rs61282106 GRCh37 Chromosome 1, 156106725: 156106725
8 LMNA NM_170707.3(LMNA): c.1745G> A (p.Arg582His) single nucleotide variant Pathogenic rs57830985 GRCh37 Chromosome 1, 156108325: 156108325
9 LMNA NM_170707.3(LMNA): c.688G> A (p.Asp230Asn) single nucleotide variant Pathogenic rs61214927 GRCh37 Chromosome 1, 156104644: 156104644
10 LMNA NM_170707.3(LMNA): c.1072G> A (p.Glu358Lys) single nucleotide variant Pathogenic rs60458016 GRCh37 Chromosome 1, 156105827: 156105827
11 LMNA NM_170707.3(LMNA): c.1045C> T (p.Arg349Trp) single nucleotide variant Pathogenic rs267607555 GRCh37 Chromosome 1, 156105800: 156105800
12 LMNA NM_005572.3(LMNA): c.1458G> T (p.Lys486Asn) single nucleotide variant Pathogenic rs59981161 GRCh37 Chromosome 1, 156106789: 156106789
13 LMNA NM_170707.3(LMNA): c.1488+5G> C single nucleotide variant Pathogenic rs267607543 GRCh37 Chromosome 1, 156106824: 156106824
14 LMNA NM_170707.3(LMNA): c.1583C> G (p.Thr528Arg) single nucleotide variant Pathogenic/Likely pathogenic rs57629361 GRCh37 Chromosome 1, 156106998: 156106998
15 LMNA NM_170707.3(LMNA): c.184C> G (p.Arg62Gly) single nucleotide variant Pathogenic rs56793579 GRCh37 Chromosome 1, 156084893: 156084893
16 LMNA NM_170707.3(LMNA): c.1961dupG (p.Thr655Asnfs) duplication Pathogenic rs863225024 GRCh37 Chromosome 1, 156108541: 156108541
17 LMNA NM_170707.3(LMNA): c.29C> T (p.Thr10Ile) single nucleotide variant Pathogenic/Likely pathogenic rs57077886 GRCh37 Chromosome 1, 156084738: 156084738

Expression for Lipodystrophy, Familial Partial, Type 2

Search GEO for disease gene expression data for Lipodystrophy, Familial Partial, Type 2.

Pathways for Lipodystrophy, Familial Partial, Type 2

Pathways related to Lipodystrophy, Familial Partial, Type 2 according to GeneCards Suite gene sharing:

(show all 12)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.44 INS IRS4 PDE3B
2
Show member pathways
12.42 INS IRS4 PDE3B
3
Show member pathways
11.88 INS LEP PDE3B
4
Show member pathways
11.75 INS IRS4 LEP
5
Show member pathways
11.55 GFPT2 INS
6 11.44 INS LEP
7
Show member pathways
11.42 INS IRS4
8 11.24 IRS4 LEP
9 11.08 LEP PDE3B
10 11.04 INS IRS4 LEP LMNA
11 11.02 INS LEP
12 10.86 INS IRS4 PDE3B

GO Terms for Lipodystrophy, Familial Partial, Type 2

Biological processes related to Lipodystrophy, Familial Partial, Type 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 glucose homeostasis GO:0042593 9.48 INS LEP
2 positive regulation of protein kinase B signaling GO:0051897 9.46 INS LEP
3 positive regulation of MAPK cascade GO:0043410 9.43 INS LEP
4 insulin receptor signaling pathway GO:0008286 9.4 INS IRS4
5 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.37 INS LEP
6 glucose metabolic process GO:0006006 9.32 INS LEP
7 negative regulation of lipid catabolic process GO:0050995 9.26 INS PDE3B
8 energy reserve metabolic process GO:0006112 9.16 GFPT2 LEP
9 positive regulation of insulin receptor signaling pathway GO:0046628 8.96 INS LEP
10 regulation of protein localization to nucleus GO:1900180 8.62 LEP LMNA

Molecular functions related to Lipodystrophy, Familial Partial, Type 2 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.96 INS LEP
2 insulin receptor binding GO:0005158 8.62 INS IRS4

Sources for Lipodystrophy, Familial Partial, Type 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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