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  • Writer's pictureThe Rare360 Editorial Team

Facing Leukocyte Adhesion Deficiency (LAD): Types, Symptoms, and Progress in Diagnosis and Treatment

Updated: Feb 2

Doctor looking at red and itchy spot on little girl's arm using a microscopic lens

Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by the inability of leukocytes (white blood cells) to migrate from circulation into sites of inflammation. This results in recurrent bacterial infections in soft tissues, such as the gums, skin, and muscles, rendering it a combined B cell and T cell immunodeficiency disorder.


The root cause of LAD is the deficiency of adhesive glycoproteins, such as integrins and selectins, on the surfaces of white blood cells (WBCs). These glycoproteins play a crucial role in facilitating cell movement, cell attachment to blood vessel walls, and cellular interaction with complement fragments. The deficiency hampers the white blood cells' ability to effectively move out of blood vessels and reach infection sites, impeding their capacity to eliminate bacteria and other foreign invaders.


For those affected by LAD, bacterial infections become apparent from the neonatal period onwards. Conditions like omphalitis, pneumonia, gingivitis, and peritonitis are not only common but can also pose life-threatening risks due to the infant's compromised ability to combat invading pathogens effectively.


Key symptoms associated with LAD include:

  • Frequent soft-tissue infections

  • Leukocytosis (high white blood cell count)

  • No pus formation

  • Delayed umbilical cord detachment

  • Gum inflammation and tooth loss

  • Poor wound healing

Understanding the Types of Leukocyte Adhesion Deficiency (LAD)

LAD stems from inherent gene variants impacting cell attachment and movement. This section explores the three types of LAD, shedding light on their genetic basis, prevalence, and distinct characteristics.

Leukocyte Adhesion Deficiency Type – I (LAD1)

LAD1, the most common form of the disorder, is caused by a mutation in the ITGB2 gene (found on chromosome 21). The mutation results in a molecular defect that causes a deficiency of the beta-2 integrin subunit (CD18).

These beta-2 integrins are crucial for the adhesion and migration of leukocytes (white blood cells), which are essential for the immune response. When these integrins are deficient or non-functional, leukocytes cannot adhere to the endothelium (inner lining) of blood vessels and migrate to sites of infection or inflammation. This results in the immune deficiency seen in LAD.

A comprehensive review of published cases reported 330 LAD-I cases between 1975-2017, with prominent instances in Iran (n=64), USA (n=52), and India (n=45).

Signs and Symptoms of LAD1

  • From birth, infants affected by LAD1 face the onset of severe bacterial infections and inflammation. Bacterial infections and inflammation predominantly manifest on the skin and mucous membranes, notably in areas like the mouth and gums.

  • An early indicator is the prolonged attachment of the umbilical cord stump, which typically separates within the first two weeks of life. However, in infants with LAD1, this detachment can be delayed until three weeks or later. Furthermore, the umbilical cord stump often becomes inflamed due to bacterial infection.

  • Children with LAD1 experience pronounced inflammation of the gums (gingivitis) and the surrounding tissue supporting the teeth (periodontitis), often leading to the loss of both primary and permanent teeth. These infections can extend to cover a substantial area.

  • A distinctive characteristic of LAD1 is the absence of pus formation at infection sites.

  • Wounds exhibit delayed healing, increasing the susceptibility to additional infections.

  • The recurrence of infections often results in a significantly shortened life expectancy for individuals with LAD1.


Leukocyte Adhesion Deficiency Type – II (LAD2) or Congenital Disorder of Glycosylation Type IIc (CDG-IIc)

LAD2 or CDG-llc is an extremely rare condition; caused by variants in the SLC35C1 gene, which affects the metabolism of fucose (a form of sugar). The condition is characterized by the absence of fucosylated carbohydrate ligands for selections.

Only a handful of cases have been reported worldwide, mainly in individuals of Middle Eastern descent.

Signs and Symptoms of LAD2 or CDG-IIc

  • Infants diagnosed with LAD2 or CDG-IIc experience recurrent bacterial infections; however, these infections and their complications are generally less severe than those seen in infants with LAD1. Common manifestations include pneumonia, chronic middle ear infections (otitis media), periodontitis, and localized infections of the skin (cellulitis).

  • These infections are typically not life-threatening, they are treatable, and their frequency tends to decrease after the age of 3.

  • Pus formation is absent at the site of infection.

  • As children grow older, a prominent complication often arises in the form of severe periodontitis.

  • They also have diminished or poor muscle tone (hypotonia), distinctive facial features, severe intellectual deficit, and severe growth deficiencies resulting in short stature.

  • Individuals with LAD2 or CDG-IIc face unique complications absent in LAD1 cases. These include a rare blood type known as the Bombay (hh) blood group.

Leukocyte Adhesion Deficiency Type – III (LAD3)

LAD3 is an extremely rare condition; caused by mutations in the FERMT3 gene. This condition is characterized by defective activation of all beta integrins (1, 2, and 3).

Less than 40 cases of LAD-III have been reported to date.

Signs and Symptoms of LAD3

  •  Individuals with LAD3 have recurrent bacterial infections mirroring the progression observed in LAD1 patients.

  • Affected individuals tend to bleed easily and profusely, especially after surgical procedures.

  • Other symptoms may include susceptibility to bruising, nosebleeds (epistaxis), bleeding from the gums (gingival), and large red- or purple-coloured spots on the skin caused by bleeding under the skin.

As an autosomal recessive disorder, it can occur in any population or ethnic group. However, the prevalence may be higher in populations with a high rate of consanguineous marriages due to the increased chance of inheriting the same recessive gene from both parents.

Learn More Research is being conducted in order to gain a better understanding as to how LAD impacts people's lives. If you or a loved one is suspected to have or has been diagnosed with LAD, you have the opportunity to include your perspectives, insights and experiences (P.I.E.) by subscribing to the Rare360 P.I.E. Program.

Navigating the Diagnostic Pathway for Leukocyte Adhesion Deficiency (LAD)

The diagnostic journey for LAD typically begins with a thorough clinical evaluation and detailed patient history. If LAD is suspected, various tests such as a complete blood count (CBC) are performed. This test can detect elevated levels of neutrophils and lymphocytes. In LAD, the CBC count typically reveals leukocytosis (WBC count >200 macro litres) without infection. With infection, leukocytosis dramatically increases (WBC counts of 400-1000 macro litres are common).

The clinical diagnosis of LAD involves detecting the absence or severe deficiency of adhesive glycoproteins on the surface of white blood cells. This is done using monoclonal antibodies and a technique called flow cytometry.

Confirmation of LAD diagnosis, specifying the subtype, is achieved through molecular genetic testing. This testing reveals characteristic variants in genes associated with each LAD type: the ITGB2 gene for LAD1, the SLC35C1 gene for LAD2, and the FERMT3 gene for LAD3. Identifying mutations in genes linked to leukocyte adhesion aids in confirming the specific LAD subtype.


Exploring Treatment Avenues for Leukocyte Adhesion Deficiency (LAD)

When it comes to managing Leukocyte Adhesion Deficiency (LAD), treatment strategies encompass several key approaches:

  •  Aggressive Antibiotic Therapy: The cornerstone of LAD treatment involves the vigorous use of antibiotics to address the recurrent infections associated with the condition. Prompt antibiotic administration is particularly effective for individuals with moderate or mild forms of LAD1 or LAD2 during acute infection episodes. Preventive or prophylactic antibiotic therapy may also be recommended for individuals with LAD1.

  • Granulocyte Transfusions: In LAD, where the deficiency or dysfunction of white blood cells compromises the immune response, granulocyte transfusions become a therapeutic approach. Granulocyte transfusions are typically considered when individuals with LAD experience severe or recurrent bacterial or fungal infections that do not respond adequately to antibiotic therapy alone. These transfusions can provide an immediate boost to the immune system, aiding in the resolution of acute infections.

  • Hematopoietic Stem Cell Transplantation: Hematopoietic stem cell transplantation is the only curative treatment option for individuals diagnosed with LAD1 and LAD3. This approach has been applied in select cases, specifically for individuals with particular genetic mutations.


For LAD2, there is currently no known cureTreatment is focused on managing the symptoms and preventing recurrent infections.  


Leukocyte Adhesion Deficiency (LAD) is a rare inherited disorder that affects the immune system. It is caused by a genetic mutation that results in impaired adhesion and migration of leukocytes, the white blood cells responsible for fighting infections.


Navigating the diagnostic pathway for LAD involves a meticulous evaluation, from clinical assessments to sophisticated molecular genetic testing. This thorough approach is crucial in confirming the specific LAD subtype and guiding treatment decisions.


Current research in Leukocyte Adhesion Deficiency (LAD) is directed towards enhancing both diagnosis and treatment, alongside delving deeper into the fundamental mechanisms of the disorder. This encompasses the exploration of novel therapies targeting integrins and advancing our comprehension of immune system functionality and regulation.

Learn More Research is being conducted in order to gain a better understanding as to how LAD impacts people's lives. If you or a loved one is suspected to have or has been diagnosed with LAD, you have the opportunity to include your perspectives, insights and experiences (P.I.E.) by subscribing to the Rare360 P.I.E. Program.














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