Abstract：
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.
To discuss the distinguishing clinical, radiological, and laboratory features of LAD-III.
This study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients.
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).
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.
To discuss the distinguishing clinical, radiological, and laboratory features of LAD-III.
This study included the clinical, radiological, and laboratory characteristics of twelve LAD-III patients.
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).
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.
摘要：
背景：由于FERMT3的突变，白细胞和血小板整联蛋白功能缺陷存在于白细胞粘附缺陷III型（LAD-III）中。此外,LAD-III中发生破骨细胞/成骨细胞功能障碍。
目的：探讨临床、放射学,和LAD-III的实验室特征。
方法：本研究包括临床，放射学,和12例LAD-III患者的实验室特征。
结果：男女比例为8/4。父母血缘比率为100%。一半的患者有类似发现的患者的家族史。出现和诊断时的中位年龄为18（1-60）天和6（1-20）个月，分别。入院时白细胞计数中位数为43,150（30,900-75,700）/μL。在8/12例患者中检测了嗜酸性粒细胞绝对计数，在6/8（75％）中发现了嗜酸性粒细胞增多。所有患者均有脓毒症病史。其他严重感染为肺炎(66.6%),脐炎（25%），骨髓炎（16.6%），牙龈炎/牙周炎（16％），脉络膜视网膜炎（8.3%），中耳炎(8.3%),腹泻（8.3%），和睑结膜感染（8.3%）。4例患者（33.3％）接受了来自HLA匹配相关供体的造血干细胞移植（HSCT），其中一人在HSCT后死亡。在最初的介绍中,4例（33.3％）患者被诊断为其他血液病，3例（P5，P7和P8）患有幼年型粒单核细胞白血病（JMML），和一个（P2）骨髓增生异常综合征（MDS）。
结论：在LAD-III中，白细胞增多,嗜酸性粒细胞增多,和骨髓检查结果可能模拟JMML和MDS等病理。除了非化脓性感染易感性，LAD-III患者表现为Glanzmann型出血性疾病.在LAD-III中,由于kindlin-3缺乏导致的整联蛋白激活缺失会破坏破骨细胞肌动蛋白细胞骨架组织。这导致骨吸收缺陷和骨硬化样放射学变化。这些是与其他LAD类型相比的独特特征。
目的：探讨临床、放射学,和LAD-III的实验室特征。
方法：本研究包括临床，放射学,和12例LAD-III患者的实验室特征。
结果：男女比例为8/4。父母血缘比率为100%。一半的患者有类似发现的患者的家族史。出现和诊断时的中位年龄为18（1-60）天和6（1-20）个月，分别。入院时白细胞计数中位数为43,150（30,900-75,700）/μL。在8/12例患者中检测了嗜酸性粒细胞绝对计数，在6/8（75％）中发现了嗜酸性粒细胞增多。所有患者均有脓毒症病史。其他严重感染为肺炎(66.6%),脐炎（25%），骨髓炎（16.6%），牙龈炎/牙周炎（16％），脉络膜视网膜炎（8.3%），中耳炎(8.3%),腹泻（8.3%），和睑结膜感染（8.3%）。4例患者（33.3％）接受了来自HLA匹配相关供体的造血干细胞移植（HSCT），其中一人在HSCT后死亡。在最初的介绍中,4例（33.3％）患者被诊断为其他血液病，3例（P5，P7和P8）患有幼年型粒单核细胞白血病（JMML），和一个（P2）骨髓增生异常综合征（MDS）。
结论：在LAD-III中，白细胞增多,嗜酸性粒细胞增多,和骨髓检查结果可能模拟JMML和MDS等病理。除了非化脓性感染易感性，LAD-III患者表现为Glanzmann型出血性疾病.在LAD-III中,由于kindlin-3缺乏导致的整联蛋白激活缺失会破坏破骨细胞肌动蛋白细胞骨架组织。这导致骨吸收缺陷和骨硬化样放射学变化。这些是与其他LAD类型相比的独特特征。
