From the Research
Leukocyte Adhesion Deficiency type 3 (LAD3) is a rare autosomal recessive primary immunodeficiency characterized by recurrent infections, bleeding disorders, and delayed umbilical cord separation, with the only curative treatment being hematopoietic stem cell transplantation (HSCT).
Clinical Presentation
LAD3 presents with severe recurrent bacterial infections, including pneumonia, sepsis, and skin abscesses, alongside significant bleeding manifestations such as petechiae, purpura, and gastrointestinal bleeding due to platelet dysfunction, as reported in a case study published in 2025 1. The clinical features of LAD3 are further supported by a study published in 2021, which highlights the importance of considering LAD3 in the differential diagnosis of patients with recurrent infections and bleeding disorders 2.
Management
Management of LAD3 requires a multidisciplinary approach, focusing on:
- Infection prevention with prophylactic antibiotics, such as trimethoprim-sulfamethoxazole at 5 mg/kg/day of the trimethoprim component divided twice daily
- Prompt treatment of acute infections with broad-spectrum antibiotics
- Platelet transfusions for bleeding episodes
- Granulocyte transfusions may be necessary during severe infections The effectiveness of HSCT in treating LAD3 is supported by a study published in 2021, which reported a 3-year overall survival estimate of 75% for LAD3 patients who underwent HSCT 2.
Epidemiology
LAD3 is a rare disorder, with only a few cases reported in the literature. The epidemiology of LAD3 is not well established, but it is believed to be an autosomal recessive disorder, meaning that affected individuals must inherit two copies of the mutated gene, one from each parent.
Molecular Basis
LAD3 results from mutations in the FERMT3 gene encoding kindlin-3, which impairs both leukocyte and platelet integrin activation, explaining the dual presentation of immunodeficiency and bleeding tendency, as reported in a study published in 2012 3. The molecular basis of LAD3 is further supported by a study published in 2015, which confirmed the presence of a mutation in the kindlin-3 gene in patients with LAD3 4.
Outcome
Without HSCT, patients with LAD3 face significant morbidity and mortality, typically not surviving beyond early childhood due to overwhelming infections or severe bleeding complications. The importance of early diagnosis and treatment of LAD3 is highlighted by a study published in 2021, which reported that patients who underwent HSCT at a younger age had better outcomes than those who underwent HSCT at an older age 2.