Three novel homozygous ITGB2 mutations among two patients with leukocyte adhesion defect type-1: Two case reports.

BACKGROUND: A leukocyte adhesion defect (LAD) is a rare primary immunodeficiency disorder. LAD type 1 (LAD-1) is the most common, which is caused by ITGB2 mutation resulting in dysfunction of ß2 integrin, which impairs leukocyte adherence to the endothelium. CASE SUMMARY: The first two cases of LAD-1 in Thailand presented with recurrent omphalitis, soft tissue infection, marked leukocytosis, and neutrophilia. One patient experienced delayed umbilical cord separation. Mutation analysis was performed by direct DNA sequencing of the ITGB2 gene. The results revealed two novel homozygous missense mutations, c.920C>T (p.Leu307Pro) in exon 8 and c.758G>A (p.Arg253His) in exon 7, and one novel homozygous nonsense mutation, c.262C>T (p.Gln88Ter) in exon 4, in the genomic DNA of the first and second patients, respectively. Heterozygous mutations were identified in the parents of both patients, suggesting a carrier status. The patients were administered intravenous antibiotics for infections with good clinical responses. Hematopoietic stem cell transplantation could not be performed due to the unavailability of matched donors. However, a significant decline in infections was observed after antibiotic prophylaxis. Several follow-up visits were conducted for both patients. They are currently 6 years old. CONCLUSION: Molecular analysis is essential for definitive diagnosis, early treatment implementation, and prevention of LAD-1 in future pregnancy.

X-Linked Chronic Granulomatous Disease: Initial Presentation with Intracranial Hemorrhage from Vitamin K Deficiency in Infant.

Vitamin K deficiency bleeding (VKDB) is a life-threatening condition and can be found in children as early as neonatal period with early onset intracranial hemorrhage (ICH). Here, we reported a 1-year-old boy who initially presented with intracranial hemorrhage secondary to vitamin K deficiency since 3 months of age and later found to have XL-CGD which was complicated by malabsorption due to severe vaccine-associated mycobacterial disease.

Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome.

PURPOSE: Patients with 22q11.2 deletion syndrome have a variable decrease in immunological parameters, especially regarding T cell counts. The aim of this study was to investigate immunological change over time and factors associated with immunological recovery among patients with 22q11.2 deletion syndrome. METHODS: Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in situ hybridization (FISH) were studied. Immunological parameters were evaluated every 6 months until patients returned to normal. Infection and vaccination histories were recorded and analyzed, and Kaplan-Meier survival curves were plotted to describe resolution of immunodeficiency. RESULTS: Forty-nine patients with an age range of 4 to 222 months were included. Twenty-five (51%) patients were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI 1.82-159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T cell numbers, which returned to normal level in 18 (60%) patients. Median age of CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three patients. T cell functions returned to normal in all patients at a median age of 1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with levels improving in four patients at 1.4 years of age. The most common infection was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at birth. Among 32 patients who had T cell defect, one patient developed BCGitis and one developed disseminated BCG. CONCLUSION: Immunodeficiencies identified among patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.

Determination of fractional exhaled nitric oxide (FENO) reference values in healthy Thai population.

BACKGROUND: Fractional exhaled nitric oxide (FENO) level is directly correlated with airway inflammation in asthma patients. The objective of this study was to define normal FENO levels in healthy Thai volunteers. METHODS: This prospective cohort study was conducted in healthy Thai volunteers aged ≥5 years. Demographic and clinical data were recorded and pulmonary function test (PFT) was performed. FENO was measured using a chemiluminescence nitric oxide analyzer. RESULTS: Seventy-nine healthy Thai volunteers with normal lung function test were included. Mean age of participants was 13 (6-47) years and 58.2% were female. All subjects had no history of allergic respiratory diseases. Mean FENO level increased with age, and the differences between age groups were statistically significant (p=0.001). The highest mean FENO level was 13.6 ppb in the 11-15 year age group, and then the FENO level gradually declined with age. The highest mean FENO level was found in the 18-24.9 body mass index (BMI) group. Significant differences were observed for FENO levels between different height groups (p=0.005) but not between different BMI groups (p=0.46). Fair correlations between FENO levels and body weight, height, FEV1, and FVC were observed. A fair correlation between FENO level and age, FENO level and FEF25%-75% was found only in volunteers ≤15 years of age. CONCLUSION: FENO level in healthy Thais increased with age until reaching maximum level (mean FENO 13.6 ppb) in the 11-15 year age group. Significant differences were observed for FENO levels between different age groups and different height groups.