Primary ciliary dyskinesia in six patients with bronchiectasis

INTRODUCTION: Primary ciliary dyskinesia [PCD] is generally considered as a rare autosomal recessive disorder. Previous studies reported various prevalence of PCD among patients with bronchiectasis. MATERIAL AND METHODS: Six PCD patients who were diagnosed during the investigation of 40 patients with bronchiectasis were enrolled in this study. Ultra structural studies for both epithelium and cilia were performed, and the deformities in detailed electron microscopic images confirmed the diagnosis of PCD. RESULTS: Four patients experienced the first symptoms shortly after the birth, 1 by the age of 1 and 1 by the age of 4 years. Except of 1 case that was diagnosed 2 months after the onset of disease, diagnosis delay was longer than 5 years in all patients. Consanguineous marriage was observed in the parents of all patients. Upper respiratory tract infections were documented for all patients. CONCLUSIONS: PCD should be considered as a probable underlying disorder in patients with bronchiectasis. Past medical history of otitis media and history of similar clinical findings in family members should raise suspicion toward PCD.INTRODUCTION: Primary ciliary dyskinesia [PCD] is generally considered as a rare autosomal recessive disorder. Previous studies reported various prevalence of PCD among patients with bronchiectasis. MATERIAL AND METHODS: Six PCD patients who were diagnosed during the investigation of 40 patients with bronchiectasis were enrolled in this study. Ultra structural studies for both epithelium and cilia were performed, and the deformities in detailed electron microscopic images confirmed the diagnosis of PCD. RESULTS: Four patients experienced the first symptoms shortly after the birth, 1 by the age of 1 and 1 by the age of 4 years. Except of 1 case that was diagnosed 2 months after the onset of disease, diagnosis delay was longer than 5 years in all patients. Consanguineous marriage was observed in the parents of all patients. Upper respiratory tract infections were documented for all patients. CONCLUSIONS: PCD should be considered as a probable underlying disorder in patients with bronchiectasis. Past medical history of otitis media and history of similar clinical findings in family members should raise suspicion toward PCD

Developing Inference Model to Diagnosis of Primary Immunodeficiency Diseases in Protégé

Primary immunodeficiency diseases (PIDs) are a genetically  heterogeneous group disorders that affect distinct components of both humoral and cellular arms of the immune system (1,2). Overlapping signs and symptoms of these diseases is a challenge for diagnosis and treatment (3,4). Awareness of the  symptoms and considering   the   possibility   of   PID   in   differential diagnosis help to rapid recognition and more appropriate treatment   (2,5).   Timely   recognition   and   treatment reduced mortality and increased lifespan and quality of life of the patients (6). Memorization of all effective criteria to diagnosis is difficult, so developing a computerized program based on diagnosis criteria, improves significantly the quality of care (7,8).To develop the inference model to the diagnosis of PIDs, ontology has been used in this study. The study focused on eight common diseases of PIDs include Common Variable Immune Deficiency (CVID), X- Linked Agammaglobulinemia (Bruton’s) (XLA), Selective IgA Deficiency (SIgA), CD40L deficiency, UNG deficiency, Isolated immunoglobulin (Ig) G Subclass deficiency, Specific antibody deficiency (SAD) with normal Ig concentrations and normal numbers of B cells, Transient Hypogammaglobulinemia of infancy (THI) with normal numbers of B cells. Based on clinical guidelines  and   medical   literature   in   PID   (9),   we designed a checklist to extract and classified most important signs and symptoms, family history, and laboratory data for eight main type of primary antibody deficiencies   (PADs).   To   evaluate   the   quality   of checklist, data for 100 cases in a different type of PADs were tested. Using frame-based ontology modeling to create the inference model and "Noy and McGuinness" method to develop the inference model. "Noy and McGuinness" method includes seven stages (10). Below we describe each stage of the method

Association Between Single Nucleotide Polymorphisms of the Interleukin-4 Gene and Atopic Dermatitis

ABSTRACT Atopic dermatitis (AD) is an inflammatory skin disease in which both genetic and environmental factors seem to be involved. Several studies investigated the association of certain genetic factors with AD in different ethnic groups, but conflicting data were obtained. This study was performed to check the possible association between single nucleotide polymorphisms (SNPs) of interleukin 4 (IL-4) and the IL-4 receptor α chain (IL-4Rα) and AD in a group of Iranian patients. The allele and genotype frequencies of genes encoding for IL-4 and IL-4Rα were investigated in 89 patients with AD in comparison with 139 healthy controls, using methods based on polymerase chain reaction sequence-specific primers. The most frequent alleles of IL-4 in patients were T at -1098 (P&lt;0.001, odds ratio (OR)=2.35), C at -590 (P&lt;0.001, OR=4.84) and C at -33 (P=0.002, OR=2.08). The most frequent genotypes of IL-4 in patients were TT, CC, and CC at positions -1098 (P&lt;0.001, OR=3.59), -590 (P&lt;0.001, OR=31.25) and -33 (P&lt;0.001, OR=3.46), respectively. We found a significant lower frequency of GT at -1098 GT, TC at -590, and TC at -33 in patients. There were no statistically significant differences in the frequency of alleles and genotypes of IL-4Rα gene at position +1902. A strong positive association was seen between TCC haplotype and AD (68% in patients vs. 23.4% in controls, P&lt;0.001, OR=8.91). We detected a significantly lower frequency of TTC, GCC, and TTT haplotypes (P&lt;0.001, OR=0.02, P&lt;0.001, OR=0.40, P&lt;0.001, OR=0.39, respectively) in patients compared to controls. A significant association between the polymorphisms of the IL-4 gene promoter at positions -1098, -590, and -33 and AD was detected in the Iranian population. Key words: atopic dermatitis; polymorphism, single nucleotide; interleukin-4 gene</p

Costs of hospital admission on primary immunodeficiency diseases

Background Primary immunodeficiency diseases (PID) are heterogeneous group of inherited disorders mainly characterized by recurrent infections leading to several times hospital admissions. The economic impact of PID is a challenging issue; therefore, this study was designed to determine the medical costs of hospitalizations in this group of patients as an indicator of the direct cost of these diseases. Methods One hundred and ten children with PID hospitalized in the Children’s Medical Center Hospital, Tehran, Iran were included in this study during Jan 2011 and Jan 2012. All direct costs during the admission period were calculated, using the hospital information system. Results Medical cost was $7.090 per patient per admission. Among them, about 1.580$ belong to drug consuming during hospitalization. Anti-infective drugs for systemic use were the most cost-consuming group of drugs, followed by alimentary tract and metabolism and blood and blood forming organs agents. Investigation of anti-infective group internally showed that immune sera and immunoglobulin and antiviral agents for systemic use consisting the most important medication for PID patients during hospital admission. Conclusion Although the results of economic evaluations in a region cannot necessarily be applied to other regions, having an overall estimation of hospital admission costs and types of drugs used during admission could be helpful in health policy system

Clinical and Laboratory Findings in Iranian Children with Cyclic Neutropenia

Cyclic neutropenia is a rare immunodeficiency syndrome, characterized by regular periodic oscillations in the circulating neutrophil count from normal to neutropenic levels through 3 weeks period, and lasting for 3-6 days. In order to determine the clinical features of cyclic neutropenia, this study was performed. Seven patients with cyclic neutropenia (3 males and 4 females), who experienced neutropenic periods every 3 weeks (5 with severe and 2 with moderate neutropenia), were investigated in this study. They had been referred to Iranian Primary Immunodeficiency Registry during 23 years (1980-2003). The range of patients' ages was from 7 to 13 years (median 11 years). The median age at the onset of the disease was 12 months (1 month- 2 years) and the median age of diagnosis was 2 (1.5-5) years, with a median diagnosis delay of 1 year (2 months- 5 years). Neutropenia was associated with leukopenia (3 patients), anemia (3 patients), and thrombocytopenia (1 patient). Patients were asymptomatic in healthy phase, but during the episode of neutropenia suffered from aphthous ulcers, abscesses and overwhelming infections. The most commonly occurred manifestations were: otitis media (6 cases), oral ulcers (5 cases), abscesses (4 cases), pneumonia (3 cases), diarrhea (3 cases), oral candidiasis (3 cases), cutaneous infections (2 cases), and periodontitis (2 cases). One of these patients subsequently died because of recurrent infections. Unusual, persistent or severe infections should be the initiating factors to search for an immune deficiency syndrome such as cyclic neutropenia, because a delay in diagnosis may result in chronic infection, irretrievable end-organ damage or even death of the patient

Individual Radiosensitivity Assessment of the Families of Ataxia-Telangiectasia Patients by G2-Checkpoint Abrogation

Objectives: Ataxia-telangiectasia (A-T) is an autosomal recessive multisystem disorder characterised by cerebellar degeneration, telangiectasia, radiation sensitivity, immunodeficiency, oxidative stress and cancer susceptibility. Epidemiological research has shown that carriers of the heterozygous ataxia-telangiectasia mutated (ATM) gene mutation are radiosensitive to ionising irradiation and have a higher risk of cancers, type 2 diabetes and atherosclerosis. However, there is currently no fast and reliable laboratory-based method to detect heterozygous ATM carriers for family screening and planning purposes. This study therefore aimed to evaluate the ability of a modified G2-assay to identify heterozygous ATM carriers in the families of A-T patients. Methods: This study took place at the Tehran University of Medical Sciences, Tehran, Iran, between February and December 2017 and included 16 A-T patients, their parents (obligate heterozygotes) and 30 healthy controls. All of the subjects underwent individual radiosensitivity (IRS) assessment using a modified caffeine-treated G2-assay with G2-checkpoint abrogation. Results: The mean IRS of the obligate ATM heterozygotes was significantly higher than the healthy controls (55.13% ± 5.84% versus 39.03% ± 6.95%; P <0.001), but significantly lower than the A-T patients (55.13% ± 5.84% versus 87.39% ± 8.29%; P = 0.001). A receiver operating characteristic (ROC) curve analysis of the G2-assay values indicated high sensitivity and specificity, with an area under the ROC curve of 0.97 (95% confidence interval: 0.95–1.00). Conclusion: The modified G2-assay demonstrated adequate precision and relatively high sensitivity and specificity in detecting heterozygous ATM carriers. Keywords: Ataxia-Telangiectasia; Chromosome Breakage; Genetic Carrier Screening; Heterozygote; Radiation Sensitivity; Sensitivity and Specificity