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Pediatrics and Neonatology (2017) 58, 99e100

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LETTER TO THE EDITOR

Leukocyte Adhesion Deficiency III: Report of


Two Siblings

Leukocyte adhesion deficiencies (LADs) are autosomal months after HSCT. The younger one was successfully
recessive immunodeficiency disorders characterized by a treated with HSCT and is still alive.
blockage in the process of leukocyte emigration to sites of LAD III is an immunodeficiency syndrome that results
inflammation.1 There are three types of this disease, each from deficiency of b1, b2, and b3 integrin activation by
affecting a different phase of the leukocyte adhesion cycle. physiological stimuli in platelets and leukocytes.3 Most
LAD III is caused by a defect in leukocyte integrin activation patients reported as having LAD III are of Turkish or Maltese
due to a mutation in the FERMT3 gene.2 The structure and origin, suggesting that this is caused by mutations inherited
expression of an integrin expression level in LAD III is from a common ancestor.
normal in contrast to that in LAD I. The patients present with delayed separation of the
We are hereby reporting on two siblings, a 5-year-old girl umbilical cord, severe and recurrent bacterial infections,
and a 3-year-old boy of Turkish origin born to asymptomatic leukocytosis, and a bleeding tendency due to dysfunctional
consanguineous parents. Both siblings had a similar clinical platelet aggregation, as in Glanzmanns thrombasthenia.
presentation consisting of delayed separation of the umbil- The most common bleeding complications are melena, and
ical cord in the neonatal period, bloody stools, hematuria, petechial lesions of the mucosa, although life-threatening
gingival bleeding, and petechia caused by severe bleeding cerebral hemorrhage may also occur. Osteopetrosis-like
tendency requiring several blood transfusions. They also bone lesions attributed to defective osteoclast function are
suffered from recurrent pulmonary infections associated another feature of the disease, which was not present in
with marked leukocytosis, but had normal platelet counts: our cases.
leukocytes: 30,800/mm3, neutrophils: 23,300/mm3, and Characterization of the molecular mechanisms of pri-
platelets: 237,000/mm3. Failure to thrive was consistent in mary immunodeficiencies is important for confirming the
both since early life; they were both below the third diagnosis as well as guiding genetic consultation and
percentile for height and weight. A molecular analysis of treatment strategy. The only curative treatment of LAD III
both siblings showed a homozygous substitution: is HSCT from a full-matched family member. However, the
ENST00000279227.9:c.1537C>T in FERMT3 gene (cytoge- management of HSCT in LAD III is difficult and the disease
netic location at 11q13.1). This homozygous variation causes presents with a high mortality risk. An early diagnosis and
a nonsensical mutation, p.Arg513Terand, called performing HSCT in early infancy using an appropriate
rs121918295, which is a known disease mutation causing LAD conditioning regimen with alkylating agents will improve
III. The parents were heterozygous for the variation. The the outcome of the disease. In our opinion, the failure of
lymphocyte subsets and immunoglobulin levels of the sib- HSCT in the first sibling may have been due to delay in
lings were within normal ranges, and > 95% of neutrophils of diagnosis.
patients expressed CD18, CD11a, and CD11b integrins, thus
ruling out an LAD I syndrome. Because hematopoietic stem
cell transplantation (HSCT) is the only proven curative Conflicts of interest
therapy for the disease,1 HSCT from fully matched foreign
donors was performed. The older sibling died due to severe The authors have no conflicts of interest relevant to this
bacteremia and graft versus host disease during the third article.

http://dx.doi.org/10.1016/j.pedneo.2016.07.006
1875-9572/Copyright 2016, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
100 Letter to the Editor

References Ruth Gershoni


Departments of Human Genetics and Pediatrics, Rambam
1. Stepensky PY, Wolach B, Gavrieli R, Rousso S, Ben Ami T,
Medical Center, Haifa, Israel
Goldman V, et al. Leukocyte adhesion deficiency type III: clin- Bruce Rappoport Faculty of Medicine, Technion e Israel
ical features and treatment with stem cell transplantation. J
Institute of Technology, Haifa, Israel
Pediatr Hematol Oncol 2015;37:264e8.
2. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S,
et al. Leukocyte adhesion deficiency-III is caused by mutations Yldz Camcoglu
in KINDLIN3 affecting integrin activation. Nat Med 2009;15: Istanbul University, Cerrahpasa Medical Faculty
306e12. Department of Pediatric Infectious Diseases, Clinical
3. Malinin NL, Zhang L, Choi J, Ciocea A, Razorenova O, Ma YQ, Immunology and Allergy, Istanbul University, Istanbul,
et al. A point mutation in KINDLIN3 ablates activation of three Turkey
integrin subfamilies in humans. Nat Med 2009;15:313e8.

Deniz Aygun* *Corresponding author. Istanbul University, Cerrahpasa


Serdar Nepesov Medical Faculty Department of Pediatric Infectious
Istanbul University, Diseases, Clinical Immunology and Allergy, Istanbul
Cerrahpasa Medical Faculty Department of University, Istanbul, Turkey.
Pediatric Infectious Diseases, Clinical Immunology and E-mail address: fdenizaygun@gmail.com (D. Aygun)
Allergy, Istanbul University,
Istanbul, Turkey

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