MCID: LKC005
MIFTS: 51

Leukocyte Adhesion Deficiency, Type Iii

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases, Blood diseases, Immune diseases

Aliases & Classifications for Leukocyte Adhesion Deficiency, Type Iii

MalaCards integrated aliases for Leukocyte Adhesion Deficiency, Type Iii:

Name: Leukocyte Adhesion Deficiency, Type Iii 54 29 13 69
Leukocyte Adhesion Deficiency Type 1 50 25 29 69
Leukocyte Adhesion Deficiency 3 12 71 14
Lymphocyte Function-Associated Antigen 1 Immunodeficiency 50 24
Leukocyte Adhesion Deficiency 1 Variant 12 71
Integrin Activation Deficiency Disease 12 71
Leukocyte Adhesion Deficiency Type Iii 12 56
Lad1v 12 71
Lad1 24 25
Iadd 12 71
Lad3 12 71
Leukocyte Adhesion Molecule Deficiency Type 1 25
Leukocyte Adhesion Deficiency-1 Variant 56
Leukocyte Adhesion Deficiency, Type 1 24
Leukocyte Adhesion Deficiency, Type 3 24
Lad3, Leukocyte Adhesion Deficiency 3 24
Leukocyte Adhesion Deficiency, Type I 52
Leukocyte Adhesion Deficiency Type I 50
Leucocyte Adhesion Deficiency Type 1 25
Lfa 1 Immunodeficiency 50
Lad-1 Variant 56
Lad1 Variant 12
Lad-Iii 56
Lad 1 50
Lad-I 50
Lad 50

Characteristics:

Orphanet epidemiological data:

56
leukocyte adhesion deficiency type iii
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: early childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
delayed wound healing
delayed separation of umbilical cord
can be treated by bone marrow transplantation


HPO:

32
leukocyte adhesion deficiency, type iii:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukocyte Adhesion Deficiency, Type Iii

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 99842disease definitionleukocyte adhesion deficiency type i (lad-i) is a form of lad (see this term) characterized by life-threatening, recurrent bacterial infections.epidemiologylad-i affects 1 individual per million.clinical descriptionusually the first signs occur in infancy or early childhood. patients present recurrent, life-threatening bacterial infections of the skin, mouth, and respiratory tract. delayed umbilical cord separation is common. skin infections may evolve into large ulcers. severe periodontitis is often present later in life and leads to early tooth loss. a lack of swelling, redness, heat, or pus is observed in the area of infection.etiologylad-i is caused by mutations in the itgb2 gene (21q22.3), encoding the beta-2-integrin, cd18, which is essential for firm adhesion of leukocytes to the endothelium. severity of the disease correlates with the degree of cd18 deficiency.diagnostic methodsdiagnosis is based on complete blood counts revealing neutrophilic leukocytosis. flow cytometric analyses reveal reduced cd18 expression on leukocytes. genetic analyses of mutations in the itgb2 gene confirm the diagnosis.differential diagnosisdifferential diagnoses include irak-4 deficiency, autosomal dominant hyper ige syndrome, chronic granulomatous disease, other primary immunodeficiencies (see these terms) and a leukemoid reaction.antenatal diagnosisantenatal diagnosis is possible through biochemical or molecular analysis of chorionic villus cells or amniocytes in affected families for which the mutation has been identified. flow cytometry can be performed at 20 weeks of gestation.genetic counselingtransmission is autosomal recessive.management and treatmentmanagement should focus on controlling infections and includes antibiotics. hematopoietic cell transplantation represents the only cure for lad-i, but gene therapy may be available in the future.prognosisprognosis depends on the severity of the disease. without hematopoietic stem cell transplantation, death in patients with severe lad-i occurs from infection within the first 2 years of life, whereas patients with a moderate form of the disease have abetter chance of surviving into adulthood. survival rate after bone marrow transplantation is 75%.visit the orphanet disease page for more resources. last updated: 5/15/2009

MalaCards based summary : Leukocyte Adhesion Deficiency, Type Iii, also known as leukocyte adhesion deficiency type 1, is related to microcephalic osteodysplastic primordial dwarfism, type ii and periosteal chondrosarcoma, and has symptoms including splenomegaly, anemia and epistaxis. An important gene associated with Leukocyte Adhesion Deficiency, Type Iii is FERMT3 (Fermitin Family Member 3), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Development Angiotensin activation of ERK. Affiliated tissues include bone, neutrophil and skin, and related phenotypes are Decreased free cholesterol and cardiovascular system

UniProtKB/Swiss-Prot : 71 Leukocyte adhesion deficiency 3: A disorder characterized by recurrent bacterial infections without pus formation, leukocytosis and major bleeding disorders.

Genetics Home Reference : 25 Leukocyte adhesion deficiency type 1 is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as viruses, bacteria, and fungi. Starting from birth, people with leukocyte adhesion deficiency type 1 develop serious bacterial and fungal infections.

OMIM : 54
Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1 (116920)-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. In LAD3, the adhesive functions of integrins on both leukocytes and platelets are disrupted, most likely due to defects in activation-dependent alterations of surface integrins that enable high-avidity binding to ligands on target cells, a process termed 'inside-out signaling' (Svensson et al., 2009; Zimmerman, 2009). (612840)

Disease Ontology : 12 A leukocyte adhesion deficiency that has material basis in mutation of the KIND3 gene on chromosome 11q13.1.

Related Diseases for Leukocyte Adhesion Deficiency, Type Iii

Diseases related to Leukocyte Adhesion Deficiency, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
id Related Disease Score Top Affiliating Genes
1 microcephalic osteodysplastic primordial dwarfism, type ii 10.5 FERMT3 ITGB2 RASGRP2
2 periosteal chondrosarcoma 10.4 ITGA2B TET1
3 leukocyte adhesion deficiency 10.1
4 marginal corneal ulcer 10.1 ITGB2 VCAM1
5 amyloidosis nodular localized cutaneous 10.0 APOA1 LPA
6 delta-1-pyrroline-5-carboxylate dehydrogenase deficiency 10.0 APOB HMGCR
7 malignant fibrous histiocytoma of bone 9.9 APOB HMGCR LPA
8 hematopoietic stem cell transplantation 9.8
9 migraine with or without aura 1 9.8 APOA1 APOB LPA
10 mental retardation, autosomal dominant 45 9.8 APOB LPA
11 bird fancier's lung 9.8 APOA1 APOB LPA
12 chondrocalcinosis with early-onset osteoarthritis 9.7 APOA1 APOB LPA
13 hyperlipidemia, familial combined 9.7 APOA1 APOB HMGCR
14 stone in bladder diverticulum 9.7 APOA1 APOB LPA
15 fish-eye disease 9.7 APOA1 APOB LPA
16 glossopharyngeal nerve disease 9.7 APOA1 APOB LPA
17 apolipoprotein c-iii deficiency 9.7 APOA1 APOB LPA
18 obesity, hyperphagia, and developmental delay 9.6 APOA1 APOB LPA
19 otospondylomegaepiphyseal dysplasia 9.5 APOA1 APOB
20 alzheimer disease-2 9.5 APOA1 APOB HMGCR LPA
21 acute apical periodontitis 9.5 APOA1 APOB HMGCR LPA
22 skin squamous cell carcinoma 9.5 APOA1 APOB HMGCR LPA
23 codas syndrome 9.4 APOA1 APOB HMGCR LPA
24 macular degeneration, age-related, 12 9.3 APOA1 APOB HMGCR LPA
25 malignant type ab thymoma 9.3 APOA1 APOB ITGA2B VCAM1
26 angina pectoris 9.3 APOA1 APOB LPA VCAM1
27 autoimmune hepatitis 9.3 APOB HMGCR LPA VCAM1
28 peripheral artery disease 9.2 APOA1 APOB LPA VCAM1
29 myelophthisic anemia 8.9 APOA1 APOB HMGCR LPA VCAM1
30 pericarditis 8.9 APOA1 APOB HMGCR LPA VCAM1
31 myocardial infarction 8.8 APOA1 APOB F2R HMGCR ITGA2B LPA
32 maturity-onset diabetes of the young 6 8.7 APOA1 APOB HMGCR LPA VCAM1
33 hepatic adenoma, somatic 8.5 APOA1 APOB LAD1 LPA VCAM1
34 dental anomalies and short stature 4.6 APOA1 APOB F2R FERMT1 FERMT2 FERMT3

Graphical network of the top 20 diseases related to Leukocyte Adhesion Deficiency, Type Iii:



Diseases related to Leukocyte Adhesion Deficiency, Type Iii

Symptoms & Phenotypes for Leukocyte Adhesion Deficiency, Type Iii

Symptoms via clinical synopsis from OMIM:

54

Abdomen- Liver:
hepatomegaly

Hematology:
anemia
bleeding tendency
defective platelet adhesion with normal platelet count

Skin Nails & Hair- Skin:
petechiae

Abdomen- Gastroin testinal:
mucosal bleeding

Abdomen- Spleen:
splenomegaly

Head And Neck- Nose:
epistaxis

Immunology:
recurrent bacterial infections
fungal infections
leukocytosis
defective neutrophil adhesion to endothelial cells

Skeletal:
osteopetrosis (in severe cases)


Clinical features from OMIM:

612840

Human phenotypes related to Leukocyte Adhesion Deficiency, Type Iii:

32 (show all 15)
id Description HPO Frequency HPO Source Accession
1 splenomegaly 32 frequent (33%) HP:0001744
2 anemia 32 HP:0001903
3 epistaxis 32 occasional (7.5%) HP:0000421
4 petechiae 32 HP:0000967
5 extramedullary hematopoiesis 32 very rare (1%) HP:0001978
6 recurrent bacterial infections 32 frequent (33%) HP:0002718
7 recurrent skin infections 32 HP:0001581
8 osteopetrosis 32 occasional (7.5%) HP:0011002
9 hepatosplenomegaly 32 frequent (33%) HP:0001433
10 leukocytosis 32 HP:0001974
11 sepsis 32 HP:0100806
12 pain 32 HP:0012531
13 subcutaneous nodule 32 HP:0001482
14 abnormality of thrombocytes 32 frequent (33%) HP:0001872
15 abnormality of the lymph nodes 32 HP:0002733

GenomeRNAi Phenotypes related to Leukocyte Adhesion Deficiency, Type Iii according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased free cholesterol GR00340-A-2 8.92 APOA1 APOB HMGCR LPA

MGI Mouse Phenotypes related to Leukocyte Adhesion Deficiency, Type Iii:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.06 APOA1 APOB F2R FERMT2 FERMT3 ITGA2B
2 cellular MP:0005384 10.03 RAP1A RAPGEF3 TET1 VCAM1 APOA1 APOB
3 homeostasis/metabolism MP:0005376 9.93 APOA1 APOB F2R FERMT1 FERMT3 HMGCR
4 immune system MP:0005387 9.7 APOB F2R FERMT1 FERMT3 ITGA2B ITGB2
5 mortality/aging MP:0010768 9.4 TET1 VCAM1 FERMT1 FERMT2 FERMT3 HMGCR

Drugs & Therapeutics for Leukocyte Adhesion Deficiency, Type Iii

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Study of Genetic and Molecular Defects in Primary Immunodeficiency Disorders Unknown status NCT00004341

Search NIH Clinical Center for Leukocyte Adhesion Deficiency, Type Iii

Genetic Tests for Leukocyte Adhesion Deficiency, Type Iii

Genetic tests related to Leukocyte Adhesion Deficiency, Type Iii:

id Genetic test Affiliating Genes
1 Leukocyte Adhesion Deficiency Type 1 29
2 Leukocyte Adhesion Deficiency, Type Iii 29
3 Leukocyte Adhesion Deficiency, Type 3 24 FERMT3
4 Leukocyte Adhesion Deficiency, Type 1 24 ITGB2

Anatomical Context for Leukocyte Adhesion Deficiency, Type Iii

MalaCards organs/tissues related to Leukocyte Adhesion Deficiency, Type Iii:

39
Bone, Neutrophil, Skin, Bone Marrow, Endothelial, Lymph Node

Publications for Leukocyte Adhesion Deficiency, Type Iii

Articles related to Leukocyte Adhesion Deficiency, Type Iii:

id Title Authors Year
1
Hematopoietic stem cell transplantation for the treatment of leukocyte adhesion deficiency type III. ( 28827066 )
2017
2
Adaptive immune defects in a patient with leukocyte adhesion deficiency type III with a novel mutation in FERMT3. ( 26359933 )
2015
3
Leukocyte Adhesion Deficiency Type III: Clinical Features and Treatment With Stem Cell Transplantation. ( 25072369 )
2014
4
Kindlin-3-independent adhesion of neutrophils from patients with leukocyte adhesion deficiency type III. ( 24342549 )
2013
5
Mice lacking the signaling molecule CalDAG-GEFI represent a model for leukocyte adhesion deficiency type III. ( 17492052 )
2007

Variations for Leukocyte Adhesion Deficiency, Type Iii

ClinVar genetic disease variations for Leukocyte Adhesion Deficiency, Type Iii:

6 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1 FERMT3 FERMT3, IVS13AS, A-G, -2 single nucleotide variant Pathogenic
2 FERMT3 NM_178443.2(FERMT3): c.48G> A (p.Trp16Ter) single nucleotide variant Pathogenic rs121918296 GRCh37 Chromosome 11, 63974884: 63974884
3 FERMT3 NM_178443.2(FERMT3): c.1729C> T (p.Arg577Ter) single nucleotide variant Pathogenic rs121918297 GRCh37 Chromosome 11, 63990566: 63990566
4 FERMT3 NM_178443.2(FERMT3): c.687G> A (p.Trp229Ter) single nucleotide variant Pathogenic rs121918298 GRCh37 Chromosome 11, 63979120: 63979120
5 FERMT3 NM_178443.2(FERMT3): c.1537C> T (p.Arg513Ter) single nucleotide variant Pathogenic rs121918295 GRCh37 Chromosome 11, 63988121: 63988121
6 FERMT3 FERMT3, GLY308ARG single nucleotide variant Pathogenic
7 FERMT3 FERMT3, 1-BP DEL, 1275T deletion Pathogenic
8 FERMT3 FERMT3, IVS2AS, A-C, -2 single nucleotide variant Pathogenic
9 ITGB2 NM_000211.4(ITGB2): c.382G> T (p.Asp128Tyr) single nucleotide variant Pathogenic rs137852615 GRCh37 Chromosome 21, 46323397: 46323397
10 ITGB2 NM_000211.4(ITGB2): c.715G> A (p.Ala239Thr) single nucleotide variant Pathogenic rs179363873 GRCh37 Chromosome 21, 46321433: 46321433
11 ITGB2 NM_000211.4(ITGB2): c.1030G> T (p.Glu344Ter) single nucleotide variant Pathogenic rs483352816 GRCh37 Chromosome 21, 46314939: 46314939
12 ITGB2 NM_000211.4(ITGB2): c.1143delC (p.Tyr382Thrfs) deletion Pathogenic rs483352817 GRCh37 Chromosome 21, 46313400: 46313400
13 ITGB2 NM_000211.4(ITGB2): c.1877+2T> C single nucleotide variant Pathogenic rs483352818 GRCh37 Chromosome 21, 46309189: 46309189
14 ITGB2 NM_000211.4(ITGB2): c.1907delA (p.Lys636Argfs) deletion Pathogenic rs483352819 GRCh37 Chromosome 21, 46308781: 46308781
15 ITGB2 NM_000211.4(ITGB2): c.576dupC (p.Asn193Glnfs) duplication Pathogenic rs483352813 GRCh37 Chromosome 21, 46321572: 46321572
16 ITGB2 NM_000211.4(ITGB2): c.843delC (p.Asn282Thrfs) deletion Pathogenic rs483352815 GRCh37 Chromosome 21, 46320289: 46320289
17 ITGB2 NM_000211.4(ITGB2): c.897+1G> A single nucleotide variant Pathogenic rs201752283 GRCh37 Chromosome 21, 46320234: 46320234
18 ITGB2 NM_000211.4(ITGB2): c.897+1G> T single nucleotide variant Pathogenic rs201752283 GRCh37 Chromosome 21, 46320234: 46320234

Expression for Leukocyte Adhesion Deficiency, Type Iii

Search GEO for disease gene expression data for Leukocyte Adhesion Deficiency, Type Iii.

Pathways for Leukocyte Adhesion Deficiency, Type Iii

Pathways related to Leukocyte Adhesion Deficiency, Type Iii according to GeneCards Suite gene sharing:

(show all 12)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.89 APOA1 APOB F2R FERMT3 ITGA2B ITGB2
2
Show member pathways
12.65 F2R ITGA2B ITGB2 RAP1A RASGRP2
3
Show member pathways
12.49 F2R ITGA2B ITGB2 RAP1A RAPGEF3 RASGRP2
4 12.22 FERMT1 FERMT2 ITGA2B ITGB2 RAP1A RAPGEF3
5
Show member pathways
11.7 ITGA2B RAP1A RAPGEF3 RASGRP2
6 11.5 ITGA2B ITGB2 RAP1A RASGRP2
7
Show member pathways
11.49 APOA1 APOB HMGCR
8 11.44 F2R FERMT3 ITGA2B RAP1A RASGRP2
9 11.33 RAP1A RAPGEF3 RASGRP2
10 11.29 APOB ITGB2 LPA
11 11.14 FERMT1 FERMT2 FERMT3 ITGB2 RAP1A VCAM1
12 10.7 RAP1A RAPGEF3 RASGRP2

GO Terms for Leukocyte Adhesion Deficiency, Type Iii

Cellular components related to Leukocyte Adhesion Deficiency, Type Iii according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 plasma membrane GO:0005886 9.97 APOA1 APOB F2R FERMT1 FERMT2 ITGA2B
2 very-low-density lipoprotein particle GO:0034361 9.46 APOA1 APOB
3 endocytic vesicle lumen GO:0071682 9.43 APOA1 APOB
4 low-density lipoprotein particle GO:0034362 9.4 APOA1 APOB
5 chylomicron GO:0042627 9.37 APOA1 APOB
6 early endosome GO:0005769 9.35 APOA1 APOB F2R RAP1A VCAM1
7 intermediate-density lipoprotein particle GO:0034363 9.26 APOA1 APOB
8 cell surface GO:0009986 9.17 APOA1 F2R FERMT2 ITGA2B ITGB2 PROM1
9 extracellular exosome GO:0070062 10.02 APOA1 APOB FERMT3 ITGA2B ITGB2 LAD1

Biological processes related to Leukocyte Adhesion Deficiency, Type Iii according to GeneCards Suite gene sharing:

(show all 17)
id Name GO ID Score Top Affiliating Genes
1 lipid transport GO:0006869 9.74 APOA1 APOB LPA
2 platelet degranulation GO:0002576 9.73 APOA1 FERMT3 ITGA2B
3 steroid metabolic process GO:0008202 9.72 APOA1 APOB HMGCR
4 cholesterol metabolic process GO:0008203 9.69 APOA1 APOB HMGCR
5 response to nutrient GO:0007584 9.65 APOA1 HMGCR VCAM1
6 establishment of endothelial barrier GO:0061028 9.54 RAP1A RAPGEF3
7 low-density lipoprotein particle remodeling GO:0034374 9.52 APOB LPA
8 cell adhesion GO:0007155 9.5 FERMT1 FERMT2 FERMT3 ITGA2B ITGB2 NRXN2
9 response to carbohydrate GO:0009743 9.49 APOB RAP1A
10 chylomicron assembly GO:0034378 9.46 APOA1 APOB
11 cell-matrix adhesion GO:0007160 9.46 FERMT2 ITGA2B ITGB2 VCAM1
12 Rap protein signal transduction GO:0032486 9.43 RAP1A RAPGEF3
13 leukocyte cell-cell adhesion GO:0007159 9.43 FERMT3 ITGB2 VCAM1
14 chylomicron remodeling GO:0034371 9.4 APOA1 APOB
15 integrin activation GO:0033622 9.37 FERMT2 FERMT3
16 lipoprotein biosynthetic process GO:0042158 9.32 APOA1 APOB
17 integrin-mediated signaling pathway GO:0007229 9.02 APOA1 FERMT2 FERMT3 ITGA2B ITGB2

Molecular functions related to Leukocyte Adhesion Deficiency, Type Iii according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 lipid binding GO:0008289 9.46 APOA1 APOB FERMT2 RASGRP2
2 lipid transporter activity GO:0005319 9.32 APOA1 APOB
3 cholesterol transporter activity GO:0017127 9.26 APOA1 APOB
4 cell adhesion molecule binding GO:0050839 9.13 ITGB2 NRXN2 VCAM1
5 Rap guanyl-nucleotide exchange factor activity GO:0017034 8.62 RAP1A RAPGEF3

Sources for Leukocyte Adhesion Deficiency, Type Iii

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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