Leukocyte adhesion deficiency type 1

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

One of the first signs of leukocyte adhesion deficiency type 1 is a delay in the detachment of the umbilical cord stump after birth. In newborns, the stump normally falls off within the first two weeks of life; but, in infants with leukocyte adhesion deficiency type 1, this separation usually occurs at three weeks or later. In addition, affected infants often have inflammation of the umbilical cord stump (omphalitis) due to a bacterial infection.

In leukocyte adhesion deficiency type 1, bacterial and fungal infections most commonly occur on the skin and mucous membranes such as the moist lining of the nose and mouth. In childhood, people with this condition develop severe inflammation of the gums (gingivitis) and other tissue around the teeth (periodontitis), which often results in the loss of both primary and permanent teeth. These infections often spread to cover a large area. A hallmark of leukocyte adhesion deficiency type 1 is the lack of pus formation at the sites of infection. In people with this condition, wounds are slow to heal, which can lead to additional infection.

Life expectancy in individuals with leukocyte adhesion deficiency type 1 is often severely shortened. Due to repeat infections, affected individuals may not survive past infancy.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ITGB2 gene cause leukocyte adhesion deficiency type 1. This gene provides instructions for making one part (the β2 subunit) of at least four different proteins known as β2 integrins. Integrins that contain the β2 subunit are found embedded in the membrane that surrounds white blood cells (leukocytes). These integrins help leukocytes gather at sites of infection or injury, where they contribute to the immune response. β2 integrins recognize signs of inflammation and attach (bind) to proteins called ligands on the lining of blood vessels. This binding leads to linkage (adhesion) of the leukocyte to the blood vessel wall. Signaling through the β2 integrins triggers the transport of the attached leukocyte across the blood vessel wall to the site of infection or injury.

ITGB2 gene mutations that cause leukocyte adhesion deficiency type 1 lead to the production of a β2 subunit that cannot bind with other subunits to form β2 integrins. Leukocytes that lack these integrins cannot attach to the blood vessel wall or cross the vessel wall to contribute to the immune response. As a result, there is a decreased response to injury and foreign invaders, such as bacteria and fungi, resulting in frequent infections, delayed wound healing, and other signs and symptoms of this condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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

Which doctor should you see?

The suggested department for discussing Leukocyte adhesion deficiency type 1 is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Leukocyte adhesion deficiency type 1. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.