Leukocyte adhesion deficiency type 1

Leukocyte adhesion deficiency type 1 is an immunodeficiency disorder that prevents white blood cells from effectively fighting infections, often leading to severe, recurrent bacterial and fungal infections starting in infancy.

Overview

Leukocyte adhesion deficiency type 1 is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. People with this condition are unable to protect the body effectively from foreign invaders such as viruses, bacteria, and fungi. Starting from birth, affected individuals develop serious bacterial and fungal infections.

Key clinical features include:

• Delayed umbilical cord detachment: The umbilical cord stump typically falls off within two weeks of birth; in affected infants, this separation usually occurs at three weeks or later.
• Omphalitis: Inflammation of the umbilical cord stump due to bacterial infection.
• Severe infections: Bacterial and fungal infections commonly occur on the skin and mucous membranes.
• Periodontitis: Severe inflammation of the gums and tissue around the teeth, often resulting in the loss of both primary and permanent teeth.
• Lack of pus: A hallmark of the condition is the absence of pus formation at infection sites.
• Slow wound healing: Wounds are slow to heal, which can lead to additional infection.

Life expectancy is often severely shortened, and affected individuals may not survive past infancy due to repeat infections.

Frequency

Leukocyte adhesion deficiency type 1 is estimated to occur in 1 per million people worldwide. At least 300 cases have been reported in the scientific literature.

Causes

Mutations in the ITGB2 gene cause leukocyte adhesion deficiency type 1. This gene provides instructions for making the β2 subunit of β2 integrins. These proteins are embedded in the membrane of white blood cells (leukocytes) and are essential for the immune response.

Normally, β2 integrins recognize signs of inflammation and allow leukocytes to attach to blood vessel walls and migrate to the site of infection or injury. Mutations in the ITGB2 gene lead to the production of a defective β2 subunit, preventing the formation of functional β2 integrins. Consequently, leukocytes cannot reach the site of infection, leading to the symptoms of the disorder.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show signs or symptoms of the condition.