Iranian Pediatric Patients Research Articles

Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism.

The embryonic development of the thyroid gland is regulated by the expression of several candidate genes which are related to congenital hypothyroidism. These genes include the numerous critical thyroid transcription factors such as NKX2.1, NKX2.5, FOXE1, and PAX8. The molecular analysis of these loci will be essential to the explanation of the participation of these transcription activators in the etiology of hypothyroidism. Among them, the role of NKX2.5 is important during the early thyroid morphogenesis and in controlling thyroidal cell differentiation and migration. Importantly, NKX2.5 change nucleotides are recognized to be central to the genesis of congenital hypothyroidism. A case-control study was conducted in 65 unrelated patients, diagnosed with primary congenital hypothyroidism and all of them were diagnosed according to the clinical presentations of thyroid hypoplasia and without cardiovascular defects. Mutational screening of the entire NKX2-5 coding sequence was performed in a cohort of pediatric patients by PCR-SSCP and direct sequencing. We identified two known variations 73C>T (R25C) and 63A>G (E21E) in patients with thyroid hypothyroidism. Both of them are located in conserved region of the gene and previously reported in cases with thyroid dysgenesis and congenital heart defects. There was a significance association between 63A>G variation with primary hypothyroidism (p=0.003). These SNPs are probably related to thyroid hypoplasia because the allele frequency of the 63A>G polymorphism was significantly different in patients and controls and also R25C variation not observed in healthy cases.

Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p=0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p<0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p<0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p<0.01) as well as IL-6 CG haplotype in healthy controls (p<0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.

Neurometabolic Diagnosis in Children who referred as Neurodevelopmental Delay (A Practical Criteria, in Iranian Pediatric Patients).

We aimed to investigate the clinical and para clinical manifestations of neuro metabolic disorders, in patients who presented by neuro developmental delay in their neuro developmental milestones. The patients diagnosed as neuro developmental delay and regression with or without seizure at the Neurology Department of Mofid Children Hospital in Tehran, Iran between 2004 and 2014 were included in our study. These patients diagnosed as neuro developmental delay by pediatric neurologists in view of diagnostic /screening neuro developmental assessment tests. The patients who completed our inclusion criteria as neuro metabolic disorders were evaluated in terms of metabolic and genetic study in referral lab. Overall, 213 patients with neurometabolic disorders were diagnosed. 54.3% of patients were male. The average age of patients was 41 +-46.1 months. 71.4% of parent's patients had consanguinity of marriages. Eighty seven percent of patients had developmental delay (or/and) regression. 55.5% of them had different type of seizures. Overall, 213 patients with 34 different neurometabolic disorders were diagnosed and classified in the 7 sub classes, consisting of: 1- organic acidemia and aminoacidopathy (122 patients), 2-storage disease (37 patients) 3- eukodystrophy (27 patients), other classes consisted: lipid oxidation disorders, urea cycle disorders, progressive myoclonic epilepsy; and peroxizomal disorders (27 patients). In patients with developmental delay or regression, with or without seizure, abnormal neurologic exam along with positive family history of similar disorder or relative parents, abnormal brain imaging with specific patterns, neurometabolic disorders should be considered as one of the important treatable diseases.

Shiga Toxigenic Escherichia coli in Iranian Pediatric Patients With and Without Diarrhea: O-Serogroups, Virulence Factors and Antimicrobial Resistance Properties.

Background:Shiga-toxigenic Escherichia coli is an important human pathogen cause of diarrhea, hemorrhagic colitis, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura in humans is a significant public health.Objectives:The aim of this study was to determine the molecular characteristics and antimicrobial resistance properties of Shiga toxigenic Escherichia coli (STEC) strains with respect to their seasonal, age and geographical distributions in Iranian pediatric patients with and without diarrhea.Patients and Methods:Four hundred and eighty swab samples were taken from pediatric patients with and without diarrhea of four major provinces of Iran. Swab samples were immediately cultured and the positive culture samples were analyzed by the polymerase chain reaction (PCR) method. Finally, antimicrobial susceptibility testing was performed using the disk diffusion method in Mueller-Hinton agar.Results:In total, 118 out of 200 diarrheic stool samples (59%) and 77 out of 280 non-diarrheic stool samples (27.5%) were positive for E. coli. Samples taken from one to ten months old cases (73.33%) and those from Shiraz province (81.13%) were the most commonly infected. Samples taken in the summer season (91.66%) were the most commonly infected. A significant difference was shown between AEEC and EHEC strains of E. coli. The genes encoding Shiga toxins and intimin protein were the most commonly detected in all strains. O26 (33.33%), O111 (18.18%) and O91 (12.12%) serogroups had the highest incidence in patients with and without diarrhea. Prevalence of the genes that encode resistance against ampicillin (CITM), gentamicin (aac(3)-IV) and tetracycline (tetA) were 80.30%, 75.75% and 65.15%, respectively. The STEC strains harbored the highest levels of resistance against ampicillin (84.84%), gentamycin (78.78%), tetracycline (50%) and sulfamethoxazole (40.90%) antibiotics. We found that 55.08% of diarrheic and 1.29% of non-diarrheic E. coli isolates were resistant to more than six antibiotics.Conclusions:Accurate control programs should be organized for antibiotic prescription especially during warmer seasons in Iran. Primary treatment of diarrheic patients with co-trimoxazole, cefotaxime and ceftriaxone is effective.

The clinical features and diagnosis of Metachromatic leukodystrophy: A case series of Iranian Pediatric Patients.

Metachromatic leukodystrophy disorder (MLD) is one of the rare neurometabolic diseases caused due to lack of saposin B and arylsulfatase A enzyme deficiency. Eighteen patients diagnosed as metachromatic leukodystrophy in the Neurology Department of Mofid Children's Hospital in Tehran, Iran between 2010 and 2014 were included in our study. The disorder was confirmed by clinical, EMG-NCV, arylsulfatase A enzyme checking and neuroimaging findings along with neurometabolic and genetic assessment from reference laboratory in Iran. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 18 patients with metachromatic leukodystrophy. From 18 patients, 80% were offspring from consanguineous marriages. A family history of metachromatic leukodystrophy disease was positive for four patients. Twelve patients had late infantile form of this disorder and six patients had juvenile form. A history of tonic type seizure was positive in 20% of the patients and tonic spasm was confirmed with clinical information. Electromyographgraphy (EMG) in 96% of patients was abnormal with demyelinating sensorimotor neuropathy pattern. MRI in all patients showed the leukodystrophic pattern as arcuate fibers sparing and subcortical rim in white matter and periventricular involvement. Our diagnosis was confirmed by EMG-NCV findings with sensorimotor neuropathy pattern and the assessment of arylsulfatase A enzyme function. MLD is an inheritance metabolic disorder, which was confirmed by the assessment of arylsulfatase A enzyme function, peripheral blood leukocyte that assessed in a referral laboratory in Iran.

Nosocomial Infections in Iranian Pediatric Patients With Burn Injuries: A Review

Context: Nosocomial infections (NIs) are the most common life-threatening complications and leading cause of morbidity and mortality in pediatric patients with burn injuries. It is estimated that annually two million infections, 90000 deaths, and 4.5 billion USD in excess healthcare costs are imposed by NIs. Herein, we reviewed the articles related to NIs in Iranian pediatric patients with burn injuries. Evidence Acquisition: A review of epidemiologic studies on NI in pediatric patients with burn injuries in Iran was performed by searching studies indexed in PubMed, Google scholar, Iranmedex, Magiran, SID databases, published in English language in 2014. Keywords for searching included “Nosocomial Infections”, “Hospital- acquired infection”, “Healthcare- associated infections”, “burn”, “children”, “pediatric”, and “Iran”. All articles related to NIs in pediatric patients with burn injuries or about general population with burn injuries, which included pediatric population up to the age 18 years in Iran, were included. Articles out of the definition for age group or lack of significant data, outpatients, and patients selected for reconstructive surgeries were excluded. Results: Of 43 reviewed articles, nine eligible articles were selected. The male to female ratio was 1.6:1. The age ranged from birth to 18 years with the mean of 3.4 years. Overall incidence of NIs was 20.94%. Pseudomonas aeruginosa (30.39%), Klebsiella pneumonia (17.54%), Acinetobacter (17.47%), and Staphylococcus aureus (14.98%) were the most common prominent isolates with high antibiotic resistance isolated from the cultures of different sites of infections including burn wound. Vancomycin was highly specific antibiotic against Gram-positive bacteria isolates. All spices of Acinetobacter were multidrug resistant. The mean of mortality rate was 8.75%. Conclusions: In spite of higher incidence of NIs in children with burn injuries, there are no well-described benchmark rates in this population. Further epidemiologic studies to identify knowledge gap regarding NIs in pediatric patients with burn in Iran is recommended.

Clinical Manifestations, Laboratory Findings and Disease Course of Iranian Pediatric Patients Diagnosed with Hepatitis A Infection

Background: According to some provincial reports, prevalence of hepatitis A has had a decreasing trend during the past decade in Iran. We aimed to overview clinical manifestations and laboratory findings of Iranian pediatric patients diagnosed with hepatitis A infection. Materials and Methods: This retrospective study was performed on 162 consecutive pediatric cases of hepatitis A infection. Data were collected by reviewing hospital records on admission to hospital. Results: The mean±SD age of participants was 9.90±4.08 years and 55.6% were boys. Regarding clinical manifestations, the most frequent symptom was jaundice. Fever was more prevalent in girls than in boys; whereas, abdominal tenderness was more prevalent in boys compared to girls. There was no difference in the prevalence of other clinical indices as well as in laboratory parameters between two sexes. Diarrhea was significantly more frequent in children younger than 2 years compared with other age subgroups. However, abdominal tenderness was more frequent in older patients compared to younger children. Regarding laboratory parameters, except for serum direct bilirubin that raised less in children younger than 2 years, the prevalence of other biochemical markers abnormality was comparable in different age groups. Conclusion: Hepatitis A infection is a common finding among Iranian children that equally occurs in boys and girls, while commonly appearing in children aged 7-18 years. The most frequent abnormal changes in laboratory parameters refer to change of liver enzymes, serum bilirubin, serum albumin and coagulated indices. [GMJ.2015;4(2):90-95]

Homocystinuria: Diagnosis and Neuroimaging Findings of Iranian Pediatric patients.

Homocystinuria is a neurometabolic diseases characterized by symptoms include Neurodevelopmental delay, lens dislocation, long limbs and thrombosis. The patients who were diagnosed as homocystinuria marfaniod habits, seizure in the Neurology Department of Mofid Children's Hospital in Tehran, Iran between 2004 and 2014 were included in our study. The disorder was confirmed by clinical andneuroimaging findings along withneurometabolic and genetic assessment fromreference laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 20 patients with homocystinuria. A total of 75% of patients were offspring from consanguineous marriages. A total of 95% of patients had a history of developmental delay and 40% had developmental regression. A total of 75% had seizures from these 45% showed refractory seizures. Seizures among 13 patients werecontrolled with suitable homocystinuria treatment. The patients with homocystinuriawere followed for approximately 10 years and the follow-ups showed that the patients with an early diagnosis and treatment had more favorable clinical responses for growth index, controlled refractory seizures, neurodevelopmental status, and neuroimaging findings. Neuroimaging findings include brain atrophy and/or white matter involvement. According to the results of this study, we suggest that early assessment and detectionplayan important role in the prevention of disease progression and clinical signs. Homocystinuria in patients with a positive family history, developmental delays, or regression, refractory, or recurrent seizures should take precedence over other causes.

Food allergy among Iranian children with inflammatory bowel disease: A preliminary report.

Background:Evidence has shown a link between allergic disease and inflammatory bowel diseases (IBDs). We investigated food allergy in Iranian pediatric IBD patients.Materials and Methods:A cross-sectional study was conducted on a consecutive sample of children with newly diagnosed IBD referring to Mofid Children's University Hospital in Tehran (Iran) between November 2013 and March 2015. Data on age, gender, history of cow's milk allergy (CMA), IBD type, routine laboratory tests, and colonoscopic and histopathological findings were gathered. Food allergy was assessed with the skin prick test (SPT).Results:A total of 28 patients including 19 ulcerative colitis (UC), 7 Cronh's disease (CD), and two with unclassified colitis with a mean age of 8.3 ± 4.4 years. (57.1% females, 42.9% were studied. History of CMA was present in eight patients (28.6%). Seventeen patients (60.7%) had at least one food allergy (68.4% of UC vs. 42.9% of CD, P = 0.230). Ten patients (35.7%) had multiple food allergies (36.8% of UC vs. 42.9% of CD, P > 0.999). Common allergic foods were cow's milk (28.6%), beef, seafood, albumen, wheat, and walnuts (each 10.7%), and peanuts and chestnuts (each 7.1%). The SPT showed CMA in 68.4% (8/17) of UC but none of the CD patients (P = 0.077).Conclusion:Food allergy is frequent in Iranian pediatric IBD patients with CMA being the most common observed allergy. The CMA seems to be more frequent in UC than in CD patients.

Characteristics of Hodgkin lymphoma in a defined group of Iranian pediatric patients.

This study was conducted to describe the characteristics of Hodgkin lymphoma in Iranian children. In a referral center for pediatric oncology (Mofid Hospital) in Tehran, patient data over a 10-year period were retrieved and recorded accordingly. Among 82 cases, 73.2% were male, 26.8% were female, and 70.7% were 5-9 years old. About 40% of patients were in stage III and 42.7% had systemic signs. Cervical nodes were commonly involved (91.5%). The most frequent histological subtype was mixed cellularity. The main hematological features were anemia (47.6%), lymphopenia (20.7%), and eosinophilia (8.7%). Survival rate was 72%, and 8.4% of patients were deceased. A 3% recurrence rate was observed in our patients. A significant relationship was found between the stage of disease and systemic signs (P<0.0005, χ2). Despite diagnosis of Hodgkin lymphoma in many children in Iran being made in higher stages, the mortality rate is relatively low.

The prevalence of aminoglycoside-modifying enzymes among coagulase negative staphylococci in Iranian pediatric patients.

In spite of widespread emergence of aminoglycoside resistance, these drugs are still used in the treatment of staphylococcal infections. This study aimed to investigate the distribution of aminoglycoside resistance and genes encoding aminoglycoside - modifying enzymes (AMEs) as well as Staphylococcal Cassette Chromosome mec (SCCmec) type in coagulase negative staphylococci (CoNS) in pediatric patients. Totally, 93 CoNS isolates were examined for susceptibility to aminoglycosides using disk diffusion and/or E-test methods. AMEs genes and SCCmec types were detected using multiplex PCR. Strain typing was performed using repetitive extragenic palindromic (REP) - PCR assay. The non-susceptibility rates to kanamycin, tobramycin, gentamicin, amikacin and netilmicin were 73%, 59%, 49.5%, 16% and 7.5%, respectively. aac(6')-Ie-aph(2″)-Ia, ant(4')-Ia and aph(3')-IIIa were encountered in 56 (60.2%), 38 (40.8%) and 18 (19.3%) isolates, respectively. In aac(6')-Ie-aph(2″)-Ia- positive isolates, the non- susceptibility rates to kanamycin, gentamicin, tobramycin, amikacin and netilmicin were 83%, 74%, 73%, 49% and 43%, respectively. SCCmec types included type IV (n = 31), I (n = 17), II (n = 5), III (n = 4), and V (n = 2). Three isolates had two types; I + III (n = 2) and III + IV (n = 1) whereas 11 isolates were non-typeable. AMEs genes carriers were distributed frequently into type IV. We found diverse fingerprint patterns among our isolates. In conclusion, there was a strong correlation between alarming rate of aminoglycoside resistance and methicillin resistance. Discordances between phenotypic and genotypic detection of aminoglycoside resistance were discernible. AMEs genes might be related to SCCmec types.

Virulence Factors and O-Serogroups Profiles of Uropathogenic Escherichia Coli Isolated from Iranian Pediatric Patients

Background:Uropathogenic Escherichia coli O- Serogroups with their virulence factors are the most prevalent causes of UTIs.Objectives:The present investigation was performed to study the virulence factors and O-Serogroups profiles of UPEC isolated from Iranian pediatric patients.Patients and Methods:This cross sectional investigation was performed on 100 urine samples collected from hospitalized pediatrics of Baqiyatallah Hospital, Tehran, Iran. Midstream urine was collected to decrease potential bacterial, cellular and artifactual contamination. All samples were cultured and those with positive results were subjected to polymerase chain reactions to detect pap, cnf1, afa, sfa and hlyA genes and various O- Serogroups.Results:We found that 37.5% of boys and 75% of girls had positive results for Escherichia coli. We also found that O1 (19.33%), O2 (13.33%), O6 (13.33%), O4 (11.66%), and O18 (11.66 %) were the most commonly detected Serogroups. Totally, the serogroup of 5% of all strains were not detected. In addition, all of these O- Serogroups were pap+, cnf1+, hlyA+, and afa+. Totally, pap (70 %), cnf1 (56.66 %), and hlyA (43.33 %) were the most commonly detected virulence genes in the both studied groups of children. The sfa (30 %) and afa (26.66 %) genes had the lowest incidence rates.Conclusions:Special health care should be performed on UTIs management in Iranian pediatric patients. Extended researches should be performed to evaluate relation between other O-Serogroups and virulent genes.

Multidrug Resistance-Associated Protein 1 Predicts Relapse in Iranian Childhood Acute Lymphoblastic Leukemia

Multidrug resistance (MDR) is a main cause of failure in the chemotherapeutic treatment of malignant disorders. One of the well-known genes responsible for drug resistance encodes the multidrug resistance- associated protein (MRP1). The association of MRP1 with clinical drug resistance has not systematically been investigated in Iranian pediatric leukemia patients. We therefore applied real-time RT-PCR technology to study the association between the MRP1 gene and MDR phenotype in Iranian pediatric leukemia patients. We found that overexpression of MRP1 occurred in most Iranian pediatric leukemia patients at relapse. However, no relation between MRP1 mRNA levels and other clinical characteristics, including cytogenetic subgroups and FAB subtypes, was found.

IL-1β (−511T/C) gene polymorphism not IL-1β (+3953T/C) and LT-α (+252A/G) gene variants confers susceptibility to visceral leishmaniasis

Lymphotoxin-α (LT-α) and interleukin-1beta (IL-1β) are proinflammatory cytokines playing important roles in immunity against Leishmania infection and the outcome of the disease. As cytokine productions are under the genetic control, this study tried to find any probable relationship between these cytokine gene polymorphisms and the susceptibility to visceral leishmaniasis in Iranian pediatric patients. Ninety-five pediatric patients involved with visceral leishmaniasis and 128 non-relative healthy people, from the same area as the patients, were genotyped for LT-α (+252A/G) and IL-1β (+3953T/C and -511T/C) gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was not found any significant differences in allele and genotype frequencies of LT-α (+252A/G) and IL-1β (+3953) among the study groups. However, the frequency of IL-1β -511TT genotype was higher in the controls (P = 0.0004) while the frequency of IL-1β -511CC genotype and C allele were higher in the patients (P = 0.008 and P = 0.00006, respectively). Furthermore, IL-1β CC (-511/+3953) haplotype was more frequent in VL patients compared with the controls (P = 0.0002) and the distribution of TT haplotype was higher in the controls compared with the patients (P = 0.003). In conclusion, based on the results, IL-1β -511C allele, CC genotype and CC (-511/+3953) haplotype could be considered as the susceptibility factors for visceral leishmaniasis while IL-1β -511TT genotype, T allele and TT haplotype (-511/+3953) might be counted as the influential factors for resistance to the disease.

NOD2 Sequencing in Iranian Children with Crohn’s Disease

Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Although the exact etiology of disease is still unknown, mutations in the CARD15/NOD2 gene have been reported in association with CD in several studies. This study was performed to determine whether the CARD15/NOD2 gene confers susceptibility to Iranian pediatric patients with CD. All 12 coding exons of the CARD15/NOD2 gene were sequenced in 16 enrolled pediatric onset CD patients. Sequencing of the CARD15/NOD2 gene showed no mutation. However, two patients harbored polymorphisms within this gene. A heterozygous single nucleotide polymorphism rs3135500 C > Y in the exon 12.3 was detected in a 10-year-old girl with mild severity of CD and history of rectovaginal and perianal fistula, and multiple skin tags. The other 5-year-old boy with moderate to severe CD and a history of perianal fissures and oral candidiasis harbored heterozygous single nucleotide polymorphisms in exons 4.1 and 12.1. The results of the present study show that the CARD15/NOD2 mutations in Iranian patients with pediatric onset CD are not responsible for the pathogenesis of disease.

Safety and efficacy of terbinafine in a pediatric Iranian cohort of patients with Tinea capitis

Background and objectives Tinea capitis is a common infection of the scalp and hair shaft caused by dermatophyte fungi that mainly affects prepubescent children. Systemic therapy is required for treatment and to prevent spread. The aim of present study was to assess the effect of terbinafine for Tinea capitis treatment in children. Methods Thirty Iranian pediatric patients with a clinical diagnosis of Tinea capitis were enrolled in the study. The Study was conducted in a general and referral teaching hospital (Imam Medical Centre – Tehran, Iran) from 2006 to 2007. Eligible patients with less than 20 kg of body weight were given 62.5 mg terbinafine, and for patients between 20 and 40 kg the dose was 125 mg, on the first visit. All patients had the second clinical visit and second samples for microscopic study were taken. For each patient, direct mycology test (KOH test) and mycological culture were carried out before the study was started and after second, fourth, fifth, sixth and eighth weeks. Probable drug’s adverse effects were also recorded. Results Based on the results of mycological culture of patients’ lesions, Microsporum canis and Trichophyton sheonlini were considered as major causes of Tinea capitis in these children. Out of 30 study patients, KOH test of 93% in the 5th week and 100% in the 6th week was negative. All patients healed completely from signs of infection, after six weeks. Also, no severe side effects were seen in any patients. Conclusion According to the results of this study, the use of terbinafine is an effective therapy in Iranian cases of Tinea capitis in children without severe side effects.