Leukocyte Adhesion Deficiency, Type Iii

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OMIM 57 612840 Disease Ontology 12 DOID:0110910 DOID:0110912 Orphanet 59 ORPHA99844 ICD10 via Orphanet 34 D84.8

UMLS via Orphanet 74 C2748536 MedGen 42 C2748536 SNOMED-CT via HPO 69 258211005 12441001 249366005 271813007 50091001 36760000 95325000 16294009 127566005 32942005 165397008 271737000 111583006 124958002 42952007 80515008 428875002 1926006 367489004 22253000 more UMLS 73 C2748536 C0398738

NIH Rare Diseases : ⁵³ 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.

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 congenital disorder of glycosylation, type iic, and has symptoms including petechiae of skin An important gene associated with Leukocyte Adhesion Deficiency, Type Iii is FERMT3 (Fermitin Family Member 3), and among its related pathways/superpathways are Development Angiotensin activation of ERK and Blood-Brain Barrier and Immune Cell Transmigration: VCAM-1/CD106 Signaling Pathways. Affiliated tissues include skin, bone and neutrophil, and related phenotypes are epistaxis and petechiae

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

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 : ⁵⁷ 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 : ⁷⁵ Leukocyte adhesion deficiency 3: A disorder characterized by recurrent bacterial infections without pus formation, leukocytosis and major bleeding disorders.

Clinical features from OMIM:

612840

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