MCID: LKC005
MIFTS: 47

Leukocyte Adhesion Deficiency, Type Iii

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

Aliases & Classifications for Leukocyte Adhesion Deficiency, Type Iii

MalaCards integrated aliases for Leukocyte Adhesion Deficiency, Type Iii:

Name: Leukocyte Adhesion Deficiency, Type Iii 53 28 13 69
Leukocyte Adhesion Deficiency Type 1 49 24 28 69
Leukocyte Adhesion Deficiency 3 53 12 71 14
Leukocyte Adhesion Deficiency 1 Variant 53 12 71
Integrin Activation Deficiency Disease 53 12 71
Lad1v 53 12 71
Lad3 53 12 71
Iadd 53 12 71
Lymphocyte Function-Associated Antigen 1 Immunodeficiency 12 49
Leukocyte Adhesion Deficiency Type Iii 12 55
Leukocyte Adhesion Deficiency Type I 12 49
Leukocyte Adhesion Deficiency 1 12 14
Lad1 12 24
Leukocyte Adhesion Deficiency 1 Variant; Lad1v 53
Leukocyte Adhesion Molecule Deficiency Type 1 24
Integrin Activation Deficiency Disease; Iadd 53
Leukocyte Adhesion Deficiency-1 Variant 55
Leucocyte Adhesion Deficiency Type 1 24
Lfa 1 Immunodeficiency 49
Lfa1 Immunodeficiency 12
Lad-1 Variant 55
Lad1 Variant 12
Lad-Iii 55
Lad 1 49
Lad-I 49
Lad 49

Characteristics:

Orphanet epidemiological data:

55
leukocyte adhesion deficiency type iii
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive

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


HPO:

31
leukocyte adhesion deficiency, type iii:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Leukocyte Adhesion Deficiency, Type Iii

NIH Rare Diseases : 49 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 leukocyte adhesion deficiency, type i and kindler syndrome, and has symptoms including pain, hepatosplenomegaly and splenomegaly. 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 skin, bone and neutrophil, and related phenotypes are cardiovascular system and hematopoietic system

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

Genetics Home Reference : 24 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 : 53 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)

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

Related Diseases for Leukocyte Adhesion Deficiency, Type Iii

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:

53
Abdomen Spleen:
splenomegaly

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

Head And Neck Nose:
epistaxis

Abdomen Gastroin testinal:
mucosal bleeding

Abdomen Liver:
hepatomegaly

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

Skin Nails Hair Skin:
petechiae

Skeletal:
osteopetrosis (in severe cases)


Clinical features from OMIM:

612840

Human phenotypes related to Leukocyte Adhesion Deficiency, Type Iii:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 pain 31 HP:0012531
2 hepatosplenomegaly 31 frequent (33%) HP:0001433
3 splenomegaly 31 frequent (33%) HP:0001744
4 hepatomegaly 31 HP:0002240
5 subcutaneous nodule 31 HP:0001482
6 anemia 31 HP:0001903
7 leukocytosis 31 HP:0001974
8 epistaxis 31 occasional (7.5%) HP:0000421
9 sepsis 31 HP:0100806
10 petechiae 31 HP:0000967
11 recurrent bacterial infections 31 frequent (33%) HP:0002718
12 recurrent skin infections 31 HP:0001581
13 osteopetrosis 31 occasional (7.5%) HP:0011002
14 abnormality of the lymph nodes 31 HP:0002733
15 extramedullary hematopoiesis 31 very rare (1%) HP:0001978
16 abnormal thrombocyte morphology 31 frequent (33%) HP:0001872

UMLS symptoms related to Leukocyte Adhesion Deficiency, Type Iii:


petechiae of skin

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

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.73 F2R FERMT3 ITGA2B ITGB2 RAP1A SELP
2 hematopoietic system MP:0005397 9.7 F2R FERMT3 ITGA2B ITGB2 RAP1A RASGRP2
3 homeostasis/metabolism MP:0005376 9.5 F2R FERMT1 FERMT3 ITGA2B ITGB2 RASGRP2
4 immune system MP:0005387 9.23 RASGRP2 SELP F2R FERMT1 FERMT3 ITGA2B

Drugs & Therapeutics for Leukocyte Adhesion Deficiency, Type Iii

Search Clinical Trials , 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:

# Genetic test Affiliating Genes
1 Leukocyte Adhesion Deficiency, Type Iii 28 FERMT3

Anatomical Context for Leukocyte Adhesion Deficiency, Type Iii

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

38
Skin, Bone, Neutrophil, Bone Marrow, Lymph Node, Endothelial

Publications for Leukocyte Adhesion Deficiency, Type Iii

Articles related to Leukocyte Adhesion Deficiency, Type Iii:

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

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 17)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.58 F2R FERMT3 ITGA2B ITGB2 RAP1A RASGRP2
2
Show member pathways
12.48 F2R ITGA2B ITGB2 RAP1A RASGRP2
3 12.3 F2R ITGA2B ITGB2
4
Show member pathways
12.3 F2R ITGA2B ITGB2 RAP1A RASGRP2
5 12.16 FERMT1 ITGA2B ITGB2 RAP1A
6
Show member pathways
11.88 F2R ITGA2B ITGB2 RAP1A
7 11.79 ITGB2 NRXN2 SELP
8
Show member pathways
11.57 ITGA2B RAP1A RASGRP2
9 11.54 FERMT1 FERMT3 ITGB2 RAP1A
10 11.31 ITGB2 SELP
11 11.26 F2R ITGA2B
12 11.24 RAP1A RASGRP2
13 11.21 ITGB2 SELP
14 11.19 ITGB2 SELP
15 11.11 F2R FERMT3 ITGA2B RAP1A RASGRP2
16 11.05 ITGA2B ITGB2 RAP1A
17 10.64 RAP1A RASGRP2

GO Terms for Leukocyte Adhesion Deficiency, Type Iii

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

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.81 F2R FERMT1 FERMT3 ITGA2B ITGB2 NRXN2
2 cell junction GO:0030054 9.67 FERMT1 FERMT3 RAP1A RASGRP2
3 plasma membrane GO:0005886 9.56 F2R FERMT1 ITGA2B ITGB2 NRXN2 RAP1A
4 external side of plasma membrane GO:0009897 9.5 ITGA2B ITGB2 SELP
5 integrin complex GO:0008305 9.26 ITGA2B ITGB2
6 platelet alpha granule membrane GO:0031092 8.62 ITGA2B SELP

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.61 F2R RAP1A RASGRP2
2 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.46 F2R SELP
3 platelet degranulation GO:0002576 9.43 FERMT3 ITGA2B SELP
4 activation of MAPKK activity GO:0000186 9.4 F2R RAP1A
5 platelet aggregation GO:0070527 9.37 FERMT3 ITGA2B
6 integrin-mediated signaling pathway GO:0007229 9.33 FERMT3 ITGA2B ITGB2
7 positive regulation of leukocyte migration GO:0002687 9.32 ITGA2B SELP
8 leukocyte cell-cell adhesion GO:0007159 9.13 FERMT3 ITGB2 SELP
9 cell adhesion GO:0007155 9.1 FERMT1 FERMT3 ITGA2B ITGB2 NRXN2 SELP

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

# Name GO ID Score Top Affiliating Genes
1 cell adhesion molecule binding GO:0050839 8.62 ITGB2 NRXN2

Sources for Leukocyte Adhesion Deficiency, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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