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Leukocyte adhesion deficiency type 1

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Description

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.

Frequency

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.

Causes

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

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.

Other Names for This Condition

  • LAD1
  • leucocyte adhesion deficiency type 1
  • leukocyte adhesion molecule deficiency type 1

Additional Information & Resources

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Research Studies from ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Cox DP, Weathers DR. Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Jan;105(1):86-90. Epub 2007 Jul 6. Review. Citation on PubMed
  • Hanna S, Etzioni A. Leukocyte adhesion deficiencies. Ann N Y Acad Sci. 2012 Feb;1250:50-5. doi: 10.1111/j.1749-6632.2011.06389.x. Epub 2012 Jan 25. Review. Citation on PubMed
  • Harris ES, Weyrich AS, Zimmerman GA. Lessons from rare maladies: leukocyte adhesion deficiency syndromes. Curr Opin Hematol. 2013 Jan;20(1):16-25. doi: 10.1097/MOH.0b013e32835a0091. Review. Citation on PubMed or Free article on PubMed Central
  • Madkaikar M, Currimbhoy Z, Gupta M, Desai M, Rao M. Clinical profile of leukocyte adhesion deficiency type I. Indian Pediatr. 2012 Jan;49(1):43-5. Epub 2011 May 30. Citation on PubMed
  • Nagendran J, Prakash C, Anandakrishna L, Gaviappa D, Ganesh D. Leukocyte adhesion deficiency: a case report and review. J Dent Child (Chic). 2012 May-Aug;79(2):105-10. Review. Citation on PubMed
  • Parvaneh N, Mamishi S, Rezaei A, Rezaei N, Tamizifar B, Parvaneh L, Sherkat R, Ghalehbaghi B, Kashef S, Chavoshzadeh Z, Isaeian A, Ashrafi F, Aghamohammadi A. Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J Clin Immunol. 2010 Sep;30(5):756-60. doi: 10.1007/s10875-010-9433-2. Epub 2010 Jun 12. Citation on PubMed
  • Schmidt S, Moser M, Sperandio M. The molecular basis of leukocyte recruitment and its deficiencies. Mol Immunol. 2013 Aug;55(1):49-58. doi: 10.1016/j.molimm.2012.11.006. Epub 2012 Dec 17. Review. Citation on PubMed
  • van de Vijver E, Maddalena A, Sanal Ö, Holland SM, Uzel G, Madkaikar M, de Boer M, van Leeuwen K, Köker MY, Parvaneh N, Fischer A, Law SK, Klein N, Tezcan FI, Unal E, Patiroglu T, Belohradsky BH, Schwartz K, Somech R, Kuijpers TW, Roos D. Hematologically important mutations: leukocyte adhesion deficiency (first update). Blood Cells Mol Dis. 2012 Jan 15;48(1):53-61. doi: 10.1016/j.bcmd.2011.10.004. Epub 2011 Nov 30. Review. Citation on PubMed or Free article on PubMed Central
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