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


Kahraman A. B., Yaz I., Gocmen R., Aytac S., Metin A., Kilic S. Ş., ...More

Journal of clinical immunology, vol.43, no.6, pp.1250-1258, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 43 Issue: 6
  • Publication Date: 2023
  • Doi Number: 10.1007/s10875-023-01479-7
  • Journal Name: Journal of clinical immunology
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.1250-1258
  • Keywords: KINDLIN3, FERMT3, osteopetrosis, bleeding diathesis, JMML, MDS, JUVENILE MYELOMONOCYTIC LEUKEMIA, STEM-CELL TRANSPLANTATION, LAD-III, INTEGRIN, MUTATION, KINDLIN-3, DEFECTS, GENE, ACTIVATION, DIAGNOSIS
  • Bursa Uludag University Affiliated: Yes

Abstract

BackgroundLeukocyte 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.AimTo discuss the distinguishing clinical, radiological, and laboratory features of LAD-III.MethodsThis study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients.ResultsThe 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)/mu L. 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).ConclusionIn 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.