Leukocyte adhesion deficiency-1 (LAD1) is a rare and often fatal genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

 in humans.

Mechanism

LAD1 is caused by mutations in the ITGB2 gene which are inherited

Mendelian inheritance

Mendelian inheritance is a scientific description of how hereditary characteristics are passed from parent organisms to their offspring; it underlies much of genetics...

 autorecessively

Recessive

In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

. This gene encodes CD18

CD18

Integrin beta-2 is a protein that in humans is encoded by the ITGB2 gene.It is the beta subunit of four different structures:* LFA-1 * Macrophage-1 antigen * Integrin alphaXbeta2...

, a protein present in several cell surface receptor complexes found on white blood cells, including lymphocyte function-associated antigen 1 (LFA-1), complement receptor 3

Macrophage-1 antigen

Macrophage-1 antigen is a complement receptor consisting of CD11b and CD18.It binds to C3b and C4b.-Function:...

 (CR-3), and complement receptor 4

Integrin alphaXbeta2

Integrin alphaXbeta2 is a complement receptor composed of CD11c and CD18....

 (CR-4). The deficiency of LFA-1 causes neutrophils to be unable to adhere to and migrate out of blood vessels, so their counts can be high. It also impairs immune cell interaction, immune recognition, and cell-killing

Cytotoxicity

Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are a chemical substance, an immune cell or some types of venom .-Cell physiology:...

 lymphocyte functions. The lack of CR3 interferes with chemotaxis

Chemotaxis

Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...

, phagocytosis, and respiratory burst

Respiratory burst

Respiratory burst is the rapid release of reactive oxygen species from different types of cells....

.

Signs

The main sign of the disease is life-threatening, recurrent bacterial

Pathogenic bacteria

Pathogenic bacteria are bacteria that cause bacterial infection. This article deals with human pathogenic bacteria.Although the vast majority of bacteria are harmless or beneficial, quite a few bacteria are pathogenic...

 or fungal

Mycosis

A mycosis is a fungal infection of animals, including humans. Mycoses are common, and a variety of environmental and physiological conditions can contribute to the development of fungal diseases...

 soft tissue

Soft tissue

In anatomy, the term soft tissue refers to tissues that connect, support, or surround other structures and organs of the body, not being bone. Soft tissue includes tendons, ligaments, fascia, skin, fibrous tissues, fat, and synovial membranes , and muscles, nerves and blood vessels .It is sometimes...

 infections. These infections are often apparent at birth and may spread throughout the body

Systemic disease

Life-threatening disease redirects here.A systemic disease is one that affects a number of organs and tissues, or affects the body as a whole. Although most medical conditions will eventually involve multiple organs in advanced stage Life-threatening disease redirects here.A systemic disease is one...

. Other signs include delayed separation of the umbilical cord

Umbilical cord

In placental mammals, the umbilical cord is the connecting cord from the developing embryo or fetus to the placenta...

, periodontal disease

Periodontal disease

Periodontitis is a set of inflammatory diseases affecting the periodontium, i.e., the tissues that surround and support the teeth. Periodontitis involves progressive loss of the alveolar bone around the teeth, and if left untreated, can lead to the loosening and subsequent loss of teeth...

, elevated neutrophils, and impaired wound healing

Wound healing

Wound healing, or cicatrisation, is an intricate process in which the skin repairs itself after injury. In normal skin, the epidermis and dermis exists in a steady-state equilibrium, forming a protective barrier against the external environment...

, but not increased vulnerability to viral infections or cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

.

Diagnosis

Flow cytometry

Flow cytometry

Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

 with monoclonal antibodies

Monoclonal antibodies

Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....

is used to screen for deficiencies of CD18.

Treatment

Because the CD18 gene has been cloned and sequenced, this disorder is a potential candidate for gene therapy.