Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. METHODS: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. RESULTS: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. CONCLUSIONS: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

Prevalence of and risk factors for atopic dermatitis: A birth cohort study of infants in southeast Turkey.

BACKGROUND: Atopic dermatitis (AD) is most common in the first year of life. The aim of this study was to determine the prevalence of and risk factors for AD in a birth cohort of infants from southeast Turkey. METHODS: Adana Paediatric Allergy Research (ADAPAR) birth cohort study was derived from 1377 infants who were born in Cukurova University, Medical Hospital, Adana, Turkey between February 2010 and February 2011. At birth, a physical examination was performed, cord blood samples were taken, and the mother completed a baseline questionnaire that provided data on gestational conditions, family history of allergic diseases and environmental exposures. Follow-up visits scheduled at 3, 6, and 12 months included an infant physical examination and an extended questionnaire. Skin prick test was performed and food-specific IgE levels were measured at 6 and 12 months. Atopic dermatitis was diagnosed based on confirmatory examination by a physician. RESULTS: Of the 1377 infants enrolled, 59 (4.3%) were diagnosed with AD as of 12 months. Maternal allergic disease (ORs 6.28, 95% CI 1.03-38.30; p=0.046), maternal infection during gestation (ORs 3.73, 95% CI 1.25-11.09; p=0.018), and presence of food allergy (ORs 13.7, 95% CI 3.07-61.0; p=0.001) were identified as risk factors for AD. Breastfeeding and cord blood IgE levels were not identified as risk factors. CONCLUSIONS: In this cohort we found prevalence of AD as 4.3% during the first year of life. Positive family history of atopic diseases, prenatal infections and presence of food allergy are the risk factors for early presentation of AD.

Real-world patient data on immunity and COVID-19 status of patients with MPS, Gaucher, and Pompe diseases from Turkey.

BACKGROUND: COVID-19 and lysosomal storage disorders (LSDs) share a common immunological pathway as they cause the release of cytokines in a similar pattern. We aimed to evaluate the immunity status and reveal the course of COVID-19 in patients with LSDs. RESULTS: The median age of 110 patients with LSDs was 129 months (range: 21-655), and all but one patient with mucopolysaccharidosis (MPS) type III were regularly receiving enzyme replacement therapy (ERT). In 53.6% (n = 56) of the patients (23 patients with Gaucher disease [10 type III, 13 type I], 26 patients with MPS [8 type VI, 11 type IVA, 1 type III, 3 type II, and 3 type I], and 7 patients with Pompe disease), an abnormality in at least one of the autoimmunity or immunodeficiency parameters was reported. Furthermore, 12 (57%) of 21 Gaucher cases (7 type III, 5 type I), 18 (40.9%) of 44 MPS cases (9 type IVA, 5 type VI, 1 type I, 2 type II, and 1 type III), and six (66%) of nine Pompe cases were reported to involve abnormalities in at least one of the parameters related to immunodeficiency. Immunoglobulin (Ig) M and IgA levels were reported to be lower, and there were abnormalities in the lymphocyte counts and subgroups in the MPS group. ANA was reported to be positive in one patient with Gaucher type III, anti-DNA in two patients with Gaucher type I and one patient with MPS type VI, antithyroglobulin in two patients with Gaucher type I, anti-TPO in one patient with Gaucher type I, TRAB in one patient with Gaucher type I, antiphospholipid IgM in three patients with Gaucher type III and one patient with Gaucher type I, anticardiolipin IgM in one patient with Gaucher type I, one patient with Gaucher type III, and one patient with MPS type II. However, no clinical presentation was consistent with the laboratory results except for one patient with Gaucher type I disease with Hashimoto thyroiditis. Two of the four patients who survived the COVID-19 infection with mild symptoms had a diagnosis of Gaucher type I, and no abnormality was detected in their laboratory tests. The other two patients had a diagnosis of MPS types VI and II. Immune dysfunction was detected in the patient with a diagnosis of MPS type II. Four of our patients were discharged without any sequelae. CONCLUSION: Problems with immunity did not cause any noticeable clinical results. Being well protected by reducing social contact might have played a role. However, we believe that it should be borne in mind that cardiac and pulmonary involvement, as well as immune dysfunction in LSDs, may cause an increased need for intensive care because of secondary bacterial infections.

Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challenge.

BACKGROUND: There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. METHODS: Four study groups were formed: rhinitis only, without bronchial hyper-responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys-LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. RESULTS: The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T(24), the children belonging to R, R + A and AA showed significant increases in nasal eosinophils (P < 0.01, P < 0.001, and P = 0.01, respectively), sputum eosinophils (P = 0.01, P < 0.001, and P < 0.05, respectively) and blood eosinophils (P < 0.01, P < 0.001, and P < 0.05, respectively). Similarly, increases in sputum ECP (P < 0.01, P < 0.001, and P = 0.07, respectively) and sputum cys-LT levels (P = 0.07, P < 0.001, and P < 0.05, respectively) were detected in children belonging to these three groups at T(24). Sputum eosinophils significantly correlated with blood eosinophils (r = 0.54, P < 0.001) and sputum ECP (r = 0.58, P < 0.001) at T(24). CONCLUSIONS: This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms.

Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite.

BACKGROUND: Previous studies have suggested that single-allergen-specific immunotherapy (SIT) may prevent sensitization to other airborne allergens in monosensitized children. We aimed to assess the prevention of new sensitizations in monosensitized children treated with single-allergen SIT injections in comparison with monosensitized patients given appropriate pharmacologic treatment for their disease. METHODS: A total of 147 children with rhinitis and/or asthma monosensitized to house dust mite were studied; 45 patients underwent SIT with adsorbed extracts and 40 patients underwent SIT with aqueous extracts for 5 years. The control group was comprised of 62 patients given only pharmacologic treatment for at least 5 years. Skin prick tests, medication scores for rhinitis and asthma, and atopy scores according to skin prick tests were evaluated at the beginning and after 5 years of treatment. RESULTS: All groups were comparable in terms of age, sex, and disease characteristics. At the end of 5 years, 64 out of 85 (75.3%) in the SIT group showed no new sensitization, compared to 29 out of 62 children (46.7%) in the control group (P = .002). There were no differences between the SIT subgroups with regard to onset of new sensitization (P = .605). The patients developing new sensitizations had higher atopy scores (P = .002) and medication scores for both rhinitis (P = .008) and asthma (P = .013) in comparison to patients not developing new sensitizations after 5 years of SIT. CONCLUSION: According to our data, SIT has the potential to prevent the onset of new sensitizations in children with rhinitis and/or asthma monosensitized to house dust mite.

Specific allergen immunotherapy: effect on immunologic markers and clinical parameters in asthmatic children.

BACKGROUND: Specific allergen immunotherapy (SIT) is the main treatment modality for achieving long-term symptom relief in perennial allergic diseases. OBJECTIVE: The aim of this study was to evaluate the effect of 1 year of house dust mite immunotherapy on the concentrations of 3 immunologic markers: eosinophil cationic protein (ECP), nitric oxide (NO), and monocyte chemoattractant protein 1 (MCP-1). We also compared the effect on asthma symptoms and medication scores, allergen-specific bronchial challenge test, and the skin prick test. METHODS: A total of 31 mite-allergic, asthmatic children (age range, 6-16 years) were enrolled; 19 were treated with SIT and 12 controls who had refused SIT received only drug treatment. Efficacy was evaluated using serum NO, ECP, and MCP-1 levels, and asthma symptom and medication scores, allergen-specific bronchial challenge test, and skin-prick test. The results of the tests were compared at baseline and after 1 year of treatment. RESULTS: Serum NO and ECP levels decreased significantly in the SIT group (P = .01 and P = .018) compared to baseline, whereas control group values remained similar. The serum MCP-1 level decreased significantly in both the SIT and control groups (P = .009 and P = .041, respectively). The SIT group experienced significant improvement in asthma symptoms (P = .001) and medication scores (P = .001) and skin reactivity to Dermatophagoides pteronyssinus (P = .020), whereas the control group did not. The results of bronchial challenge to D pteronyssinus showed a similar pattern at baseline and after 1 year of treatment in both groups. The tolerated allergen concentration increased in both groups (P < .05). Lung function tests, total immunoglobulin (Ig) E and specific IgE to D pteronyssinus and Dermatophagoides farinae did not change after a year of treatment in either group. CONCLUSION: SIT with D pteronyssinus improves immunological and clinical parameters in mite-allergic asthmatic children after 1 year of treatment. The skin prick test may be used as a marker of efficacy of therapy.

Bronchiectasis: still a problem.

The prevalence of bronchiectasis (BR) has decreased significantly in industrialized countries, but is still commonplace in developing countries. We evaluated the causes and clinical features of BR in 23 children (13 boys (57%) and 10 girls (43%), with a mean age of 8.45 +/- 4.02 years). Infection was the major cause of BR in our region. In 8 patients, BR developed after tuberculosis or pneumonia, was associated with immune deficiency syndromes in 4 children, and with asthma in 4. Cystic fibrosis was diagnosed in 4 cases and ciliary dyskinesia in 3. In 10 patients, only one lobe was involved. Bronchiectatic lesions were most commonly found in the left lower lobe and were observed in 7 patients. Multilobar involvement was found in 13 patients. The initial treatment was primarily medical, but in 2 patients whose medical therapy failed, pulmonary resection was carried out. Three patients died from severe pulmonary infection and respiratory failure.

Neutrophil chemotaxis in children with extrinsic bronchial asthma.

Chemotactic activities of neutrophils were studied in 20 patients with bronchial asthma and 20 healthy matched controls. Chemotaxis studies were performed by the millipore filter technique using modified Boyden chambers. Mean neutrophil chemotactic activities of asthma and control groups were 17.82 +/- 7.87 microns and 14.09 +/- 6.07 microns; mean chemotactic indexes were 2.04 +/- 0.44 and 1.84 +/- 0.60 and mean random migrations were 9.53 +/- 4.61 microns and 7.93 +/- 3.33 microns, respectively. No significant difference was found between the two groups (p > 0.05).

Potential association between allergic diseases and pertussis infection in schoolchildren: results of two cross-sectional studies seven years apart.

BACKGROUND: In this study, we aimed to investigate the relationship between pertussis infections and allergic diseases in two cross-sectional questionnaire-based surveys carried out in 1997 and 2004. We also measured serum level of antibody to B. pertussis. MATERIAL AND METHODS: Two cross-sectional, questionnaire-based surveys were carried out in 1997 (n = 3164) and 2004 (n = 3728). 361 cases and 465 controls were recruited from both surveys. The skin tests were performed using standardised extracts. The level of pertussis specific IgG was measured in 136 allergic and 168 non-allergic children. RESULTS: We found that allergic diseases prevalence was significantly higher in the children suffering from pertussis infections (22.3 % fi rst and 8.8 % second survey) compared to children who did not suffer from pertussis infections (6.6 % fi rst and 4.5 % second survey) (p = 0.001 and p = 0.035, respectively). Asthma prevalence was also significantly higher in children suffering from pertussis infection (37.6 % fi rst and 26.2 % second survey) compared to children who did not suffer from pertussis (7.4 % fi rst and 5.0 % second survey) (p = 0.001 and p = 0.001, respectively). However, the mean serum levels of anti-pertussis IgG were similar in allergic and non-allergic groups (p > 0.05). CONCLUSION: Although pertussis antibody levels in atopic and non-atopic children were similar to each other, pertussis infection still seemed to have a significant effect on the development of atopic diseases.

Is there any relationship between asthma and asthma attack in children and atypical bacterial infections; Chlamydia pneumoniae, Mycoplasma pneumoniae and Helicobacter pylori.

UNLABELLED: Asthma is a chronic inflammatory airway disease characterized by variable airway obstruction and bronchial hyperresponsiveness. There are many factors affecting the development and severity of childhood asthma such as genetic predisposition, atopy, environmental factors, obesity, diet, socioeconomic status, and infectious triggers. In the present study we aimed to investigate the frequency of Mycdoplasma pneumoniae, Chlamydia pneumoniae, and Helicobacter pylori infections in asthmatic children. We investigated also whether there is a relationship between these agents and asthma attacks. MATERIAL AND METHODS: Seventy-nine asthmatic children (46 males, aged 5-15 years) were included in study. The study group was divided into two groups: group 1 consisted of 37 children with asthma attacks and group 2 consisted of 42 children with stable asthma. As a control group we studied 36 healthy children. Pulmonary function tests, skin prick tests for common allergens were performed; serum total IgE, phadiatop, specific IgM and IgG antibody levels (ELISA) for M. pneumoniae, C. pneumoniae and H. pylori were measured in all patients. RESULTS: Mycoplasma IgM and Chlamidia IgM were positive in 8.1% (3 patients) and 18.9% (7 patients) of group 1 patients, respectively. There was a statistically significant difference for Mycoplasma IgM (p = 0.031) and Chlamidia IgM (p = 0.03) between group1 and other two groups. We have not found significant difference for M. pneumoniae IgG, C. pneumoniae IgG and H. pylori IgM and IgG among groups. CONCLUSION: M. Pneumoniae and C. Pneumoniae may play a role in development of asthma exacerbations in childhood. We could not find a relationship between H. Pylori and asthma.

Comparison of conventional and rush immunotherapy with der PI in childhood respiratory allergy.

BACKGROUND: Rush immunotherapy results obtained in Der PI-sensitive children with asthma and the changes in clinical and immunological parameters were investigated. METHODS: We studied 18 patients with Der PI sensitivity. Two groups were randomized: nine patients received RIT and nine patients received conventional immunotherapy (CIT) for three years. The RIT group reached the optimal maintenance dose at the end of one week. The CIT group reached the optimal maintenance dose in approximately three months. Symptom medication scores, lung function, side effects scores, skin-prick test, diluted skin-prick test with Der PI, bronchial provocation tests with Der PI, and Der PI-specific IgE and IgG4 were investigated in baseline conditions, at six months and at the end of the third year. RESULTS: There were no significant differences between groups in age, sex, and duration of illness. Treatment was tolerated very well. However, mean side-effect scores were higher in the RIT group than in the CIT group (p < 0.005). There were no significant differences between groups in the other parameters. CONCLUSION: CIT is more advantageous than RIT in Der PI-sensitive children, although the maintenance dose was achieved more rapidly with RIT.

An infant with severe leucocyte adhesion deficiency.

A case of severe leucocyte adhesion deficiency occurred in a 6 1/2-month-old boy whose parents were first-degree cousins. Evidence of the disease first became apparent with the late separation of the umbilical cord on the 20th day and with the later development of omphalitis. The most specific finding was the very low levels of CD18 and CD11, 0.44 and 0.15%, respectively. The boy died from sepsis which occurred as an extension of necrotic lesions on the ear and in the gluteal area.

The modification in measles vaccination age as a consequence of the earlier decline of transplacentally transferred antimeasles antibodies in Turkish infants.

The maternal antibodies are gradually decreased at 9 to 12 months in infants. We determined the elimination period of maternal measles antibodies in 34 infants whose mothers had had a history of natural measles previously. Seropositivity rates at sixth and nine months of age were found to be 61.8% and 3.4%, respectively. The very low passive antibody at nine months of age may suggest the measles vaccination could be carried out earlier than just before the critical age of antibody level.

Phocomelia, ectrodactyly, skull defect and urinary system anomaly: Schinzel-phocomelia syndrome?

This report describes a girl with phocomelia of the right upper limb, ectrodactyly, sacral hypoplasia and a large skull defect, but with normal growth and mental development. Ultrasonography and intravenous pyelography showed bilateral hydronephrosis and dilated ureters. We conclude that this patient may represent Schinzel-phocomelia syndrome with additional urinary tract anomalies.

Prevalence of childhood allergic diseases in Adana, Southern Turkey.

A study to determine the prevalence of childhood asthma and other allergic diseases was done in Adana, during the period between January 1993 and January 1994. The study has been carried out on 2334 children (48.5% boys). Asthma and the other allergic diseases were recognized in 23.6% of the children. The prevalence of asthma, rhinoconjunctivitis, wheezing, and atopic dermatitis were found to be 12.9, 8.8, 8.4, and 5.0%, respectively. The symptoms of respiratory allergic diseases (asthma, rhinoconjunctivitis, wheezing) seemed to be significantly associated with the environmental factors. In conclusion, asthma and other allergic diseases constituted a major health problem for school children in Adana.

Peak expiratory flow in healthy Turkish children.

This study was conducted on 1359 healthy, non-smoking Turkish children (727M, 632F) with a mean age of 11.7 +/- 3.4 (6-17) years, in order to determine the normal values of peak expiratory flow (PEF) in Turkish children and to compare various peak-flow meters (PEFMs). PEF values increased with age and height in boys and girls. The relative increase in boys was significantly higher at puberty (p < 0.01). The values of Turkish children were found to be similar to those of Europeans. The results obtained from the three PEFMs were closely correlated.