Clinical and Osteopetrosis-Like Radiological Findings in Patients with Leukocyte Adhesion Deficiency Type III.

Abstract

BACKGROUND:

Leukocyte and platelet integrin function defects are present in leukocyte adhesion deficiency type III (LAD-III) due to mutations in FERMT3. Additionally, osteoclast/osteoblast dysfunction develops in LAD-III.

AIM:

To discuss the distinguishing clinical, radiological, and laboratory features of LAD-III.

METHODS:

This study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients.

RESULTS:

The male/female ratio was 8/4. The parental consanguinity ratio was 100%. Half of the patients had a family history of patients with similar findings. The median age at presentation and diagnosis was 18 (1-60) days and 6 (1-20) months, respectively. The median leukocyte count on admission was 43,150 (30,900-75,700)/μL. The absolute eosinophil count was tested in 8/12 patients, and eosinophilia was found in 6/8 (75%). All patients had a history of sepsis. Other severe infections were pneumonia (66.6%), omphalitis (25%), osteomyelitis (16.6%), gingivitis/periodontitis (16%), chorioretinitis (8.3%), otitis media (8.3%), diarrhea (8.3%), and palpebral conjunctiva infection (8.3%). Four patients (33.3%) received hematopoietic stem cell transplantation (HSCT) from HLA-matched-related donors, and one deceased after HSCT. At initial presentation, 4 (33.3%) patients were diagnosed with other hematologic disorders, three patients (P5, P7, and P8) with juvenile myelomonocytic leukemia (JMML), and one (P2) with myelodysplastic syndrome (MDS).

CONCLUSION:

In LAD-III, leukocytosis, eosinophilia, and bone marrow findings may mimic pathologies such as JMML and MDS. In addition to non-purulent infection susceptibility, patients with LAD-III exhibit Glanzmann-type bleeding disorder. In LAD-III, absent integrin activation due to kindlin-3 deficiency disrupts osteoclast actin cytoskeleton organization. This results in defective bone resorption and osteopetrosis-like radiological changes. These are distinctive features compared to other LAD types.

• Authors: Ayca Burcu Kahraman, Ismail Yaz, Rahsan Gocmen, Selin Aytac, Ayse Metin, Sara Sebnem Kilic, Ilhan Tezcan, Deniz Cagdas
• Journal: Journal of clinical immunology (J Clin Immunol) Vol. 43 Issue 6 Pg. 1250-1258 (08 2023) ISSN: 1573-2592 [Electronic] Netherlands
• PMID: 37014583 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Integrins

Topics

• Humans
• Male
• Female
• Osteopetrosis (diagnosis, genetics)
• Leukocyte-Adhesion Deficiency Syndrome (diagnosis, genetics)
• Integrins (physiology)
• Leukocytes (metabolism, pathology)