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

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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.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The authors received no financial support for the research.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Ayca Burcu Kahraman

  2. Ihsan Dogramaci Childrens Hospital, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Ayca Burcu Kahraman, Selin Aytac, Ilhan Tezcan & Deniz Cagdas

  3. Department of Pediatric Immunology, Institute of Child Health, Hacettepe University, Ankara, Turkey

    Ismail Yaz, Ilhan Tezcan & Deniz Cagdas

  4. Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Rahsan Gocmen

  5. Department of Pediatrics, Division of Pediatric Hematology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Selin Aytac

  6. Department of Pediatrics, Division of Immunology, University of Health Sciences, Ankara City Hospital, Ankara, Turkey

    Ayse Metin

  7. Department of Pediatrics, Division of Immunology and Rheumatology, Uludag University Faculty of Medicine, Bursa, Turkey

    Sara Sebnem Kilic

  8. Department of Pediatrics, Division of Immunology, Hacettepe University Faculty of Medicine, Ankara, Turkey

    Ilhan Tezcan & Deniz Cagdas

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  1. Ayca Burcu Kahraman
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Contributions

ABK, IY, and DC wrote the manuscript. SA, AM, SSK, and IT reviewed the clinical and laboratory findings of the patients. IY and RG reviewed the genetic and radiological findings of the patients, respectively.

Corresponding author

Correspondence to Deniz Cagdas.

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Ethical Approval

The study design was in accordance with the Helsinki Declaration and was approved by the Hacettepe University Non-interventional Clinical Research Ethics Board (2021/12-56).

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Informed consent was obtained from the patients and parents or legal guardians of the pediatric participants.

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The authors declare no competing interests.

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Key messages

• Leukocyte adhesion deficiency (LAD) type III leads to severe infections, such as sepsis, pneumonia, osteomyelitis, chorioretinitis, and cellulitis.

• Patients exhibit osteopetrosis-like bone findings and Glanzmann-type bleeding disorder.

• Leukocytosis, eosinophilia, and bone marrow findings may mimic pathologies such as JMML and MDS.

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Kahraman, A.B., Yaz, I., Gocmen, R. et al. Clinical and Osteopetrosis-Like Radiological Findings in Patients with Leukocyte Adhesion Deficiency Type III. J Clin Immunol 43, 1250–1258 (2023). https://doi.org/10.1007/s10875-023-01479-7

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