Iranian Journal of Pediatrics
Volume:21 Issue: 1, 2011

Gaucher's disease is a rare genetic disorder that results in the accumulation of cerebrosides in the liver, spleen, kidneys, lungs, brain and bone marrow. The deficiency of the specific lysosomal enzyme glucocerebrosidase is considered as causative factor. The first effective treatment for the disease, the drug Ceredase, approved in 1995, was replaced in 2001 by the drug Cerezyme®. During the period 2004-2009 in our service 11 children were hospitalized and treated for Gaucher's disease: 9 children with type 1, and 2 children with type 3 of the disease. The enzymatic examinations of the biomarker chitotriosidase were performed in Sahlgren's University Hospital, Mölndal Sweden; the DNA analysis was performed in the Children's Hospital & Regional Medical Center, Seattle, USA. We are presenting the biological and genetic molecular data of the children. In our case series, one year after the treatment started, the hemoglobin level was normalized; the platelet count was normalized in 7 patients after one year of treatment, and in 9 patients after two years of treatment. The hemorrhagic syndrome stopped after 6 months of treatment. Chitotriosidase values decreased 10-20 times the initial value, after one year of treatment and in one case the value reached the normal range. The treatment with Cerezyme® has also improved the visceral and biological signs. Anomalies of the oculomotricity were less sensitive to the treatment. According to our experience, Chitotriosidase is a sensitive and specific marker in diagnosing and monitoring Gaucher's disease. The enzyme replacement therapy through Cerezyme® is an effective and safe treatment of Gaucher's disease. Blood signs (anemia, platelet count); visceral signs (splenomegaly, hepatomegaly) as well as bone involvement showed decisive improvement under the therapy.

In beta thalassemic patients, tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body. This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients.

This double blind randomized clinical trial was carried out on 120 beta thalassemic patients older than 18 years. Patients were randomly categorized in four groups. Zinc (50mg/day) and vitamin E (400mg/day) supplements were administered for former and latter group, respectively. In the third group both supplements were administered in similar doses. The fourth (control) group received no supplement. The effect of supplementations on serum zinc and vitamin E, superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC) and body mass index (BMI) were measured at the beginning and the end of the study.

Serum zinc levels in group 1 and 3 were significantly increased (P<0.007 and P<0.005, respectively). Serum vitamin E levels in group 2 and 3 were also increased significantly (P<0.001). Mean GPX activity in group1, 2 and 3 decreased significantly (P<0.015, P<0.032 and P<0.029, respectively). Mean SOD activity and TAC did not show significant change after supplementation. BMI had significant increase in all treated groups (P<0.001).

Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage.

G-Banding followed by standard chromosome analysis is routinely used for prenatal detection of chromosomal abnormalities. In recent years, molecular cytogenetic techniques have been developed for rapid diagnosis of chromosomal abnormalities. Among these methods Quantitative Florescence Polymerase Chain Reaction (QF-PCR) has been widely used for this purpose. HHeterozygosity of short tandem repeat (STR) markers which leads to informativity is the most critical requirement for feasibility of QF-PCR. In this study we analyzed several short tandem repeats on chromosomes 13, 18, 21, X and Y on amniotic fluid samples obtained from PND candidates to diagnose conditions such as Down, Edward and Patau syndromes and also numerical sex chromosome abnormalities such as Klinefelter and Turner syndromes. Most of the analyzed STRs had acceptable heterozygosity (66.3-94.7) to be used in QF-PCR based prenatal diagnosis. Moreover, results obtained from both methods (standard karyotype and QF-PCR) for all samples were in accordance with each other. In case of using appropriate STR markers, and in certain clinical indications, QF-PCR could be used as useful technique for prenatal diagnosis even in consanguine populations such as Iranians.

Steroids are still the mainstay of management of nephrotic syndrome (NS). It was shown that steroids could impair growth and development of children. However, other clinical studies have shown conflicting results. Hospital records of 147 children with diagnosis of NS who were followed during 1988-2008 are reviewed relating to height measurements. All patients were treated with prednisolone and had been followed for at least five years. Height measures were transformed into standard deviation score (SDS). Information on dose and duration of prednisolone therapy, histological findings of biopsy as well as concomitant use of steroid-sparing agents (SSA) were also analyzed. Mean age at onset of NS was 5.94 years and at last follow-up visit 15.08 years. All patients had normal renal function during entire duration of the study. Analysis of the whole population did not show any significant alterations in the height SDS (HtSDS) between the first and the last follow-up visit (P=0.5; -0.76±2.0 vs. -0.89±2.05 respectively). The patients were divided into two subgroups. Subgroup A, which achieved growth improvement, was composed of 62 children (initial HtSDS -1.63; final HtSDS -0.08; P<0.001) and subgroup B, that showed growth retardation, included 85 children (initial HtSDS -0.13; final HtSDS -1.59; P<0.001). No statistically significant retardation of linear growth was observed in the study population as a group following treatment with prednisolone according to the guidelines of ISKDC. Although about 62 subjects had growth retardation, children treated with prednisolone were not different from those who had increased growth.

The aim of this study was to evaluate the bilirubin albumin (B/A) ratio in comparison with total serum bilirubin (TSB) for predicting acute bilirubin-induced neurologic dysfunction (BIND). Fifty two term and near term neonates requiring phototherapy and exchange transfusion for severe hyperbilirubinemia in Children's Medical Center, Tehran, Iran, during September 2007 to September 2008, were evaluated. Serum albumin and bilirubin were measured at admission. All neonates were evaluated for acute BIND based on clinical findings. Acute BIND developed in 5 (3.8%) neonates. B/A ratio in patients with BIND was significantly higher than in patients without BIND (P<0.001). Receiver operation characteristics (ROC) analysis identified a TSB cut off value of 25 mg/dL [area under the curve (AUC) 0.945] with a sensitivity of 100% and specificity of 85%. Also, according to the ROC curve, B/A ratio cut off value for predicting acute BIND was 8 (bil mg/al g) (AUC 0.957) with sensitivity of 100% and specificity of 94%. Based on our results, we suggest using B/A ratio in conjunction with TSB. This can improve the specificity and prevent unnecessary invasive therapy such as exchange transfusion in icteric neonates.

Clinical features of Iranian children with celiac disease (CD) are still unknown and there is scant information about atypical presentation of celiac disease from Iran. The aim of this study was to determine prevalence of CD in Iranian children presenting with functional abdominal pain (FAP). In this cross-sectional study, 301 children affected by FAP were screened for CD by anti-tissue transglutaminase antibody (tTG IgA). IgA antibody was also measured to exclude IgA deficiency. The antibodies were measured by enzyme linked immunosorbent assay. Diagnosis of CD was confirmed by duodenal biopsy that was scored according to the Marsh classification in cases with abnormal titer of tTG antibody. A total of 301 children (138 males, 163 females) with FAP were studied. Endoscopic duodenal biopsy was taken for patients with positive and borderline tTG test. Two out of 301 cases were IgA deficient and celiac disease was suspected for one of them based on histological findings. Four out of 299 patients with normal IgA had abnormal tTG titer; intermediate ranges (16-23 U/ml) were detected in 1 and positive ranges (≥24 U/ml) in 3 cases. CD was suggested in all patients with abnormal titer of tTG (1.33%) based on histological findings. The prevalence of celiac disease in children with FAP is estimated 1.3% (nearly 2 times higher than in normal population) in Iran.

Tuberculosis (TB) is an important infectious disease worldwide. Tuberculin skin test (TST) is the standard test for diagnosis of tuberculosis infection; Bacillus Calmette-Guerin (BCG) vaccination at birth has effects on this test. The aim of this study was to determine the prevalence of positive TST cases among 7- to 11-year-old primary school children and also to follow test-positive individuals for a five-year period. TST was performed on 10.184 children aged 7-11 years sampled by cluster random method in Kermanshah, West Iran. Those who had a positive test result (i.e. an induration of ≥15 mm following 72 hours of injecting 0.1 ml of 5 tuberculin units of purified protein derivative from Mycobacterium tuberculosis) were followed for five years to determine the presence of active TB. Also tuberculin positive rates at cut-off points of 10 mm and ≥15 mm for boys and girls and at different ages were derived and compared using the chi-squared test. Of 10.184 studied subjects, 830 (8.15%) cases showed positive TST. This rate was 8.7% in boys and 7.8% in girls (P=0.1). A significant linear trend was found between the tuberculin positive rates and age at all cut-off points (P<0.001). No active TB was detected during 5-year follow-up. The rate of positive TST cases in primary school children in Kermanshah, Iran was 8.15% with no new cases of active tuberculosis detection within five-year follow-up.

Air leak syndromes including pneumothorax, pneumomediastinum and pulmonary interstitial emphysema are frequent in neonatal period. Mechanical ventilation with positive pressure is one of the most common causes of these syndromes. The aim of this study was to evaluate predisposing factors and incidence of pneumothorax in newborns under mechanical ventilation. This descriptive cross sectional study was performed in 400 newborns under mechanical ventilation in intensive care unit of a teaching hospital in Iran from April 2004 to December 2008. Predisposing factors leading to ventilation and incidence of air leak syndromes were studied. Sex, gestational age, birth weight, type of delivery, history of surfactant replacement therapy, ventilator settings and mortality rate were recorded. Statistical analysis was done using SPSS software. Univariate analysis and regression analysis were considered. Among 400 patients under mechanical ventilation, 102 neonates developed pneumothorax (26%). Fifty six (54.9%) of them were boys and 46 (45.1%) girls. 54.9% of newborns with pneumothorax were preterm and 45.1% term. Birth weight less than 2500g was recorded in 59.8%. Fifty two percent of these neonates were born by cesarean section vs. 32% of newborns without pneumothorax. The most common type (62.7%) of ventilation leading to pneumothorax was Inspiratory Positive Pressure Ventilation (IPPV). Surfactant replacement therapy was recorded in 32.4% of cases with pneumothorax compared to 60.4% of neonates under ventilation without pneumothorax, which was significantly different (P= 0.017). In newborns surfactant replacement therapy can reduce the risk of pneumothorax caused by mechanical ventilation.

Cystic fibrosis and its distribution vary widely in different countries and/or ethnic groups. Common CFTR mutations were reported from Iran, but the northern population was not or underrepresented in those studies. The aim of this study was to determine the frequency of common CFTR mutations in children from northern Iran. Thirty unrelated Iranian cystic fibrosis patients aged less than 11 years and living in Mazandaran province were screened for 5 common CFTR gene mutations. deltaF508, N1303K, G542X, R347H and W1282X using Reverse Dot Blot method. Only one mutation, DeltaF508, was found in 7 patients accounting for 21.7% (13/60) of alleles. These findings can be used for planning future screening and appropriate genetic counseling programs in Iranian CF families.

Acute respiratory infection (ARI) is the major cause of morbidity and mortality in children worldwide. Human respiratory syncytial virus (HRSV) is main viral agent of ARI in infants and young children in terms of effect and prevalence. The aim of this study was to investigate HRSV genotypes during one season in Iran. In this cross-sectional study, 107 throat swabs were collected from children less than 5 years of age with acute respiratory infection from October to December 2009. The respiratory samples were obtained from several provinces: Tehran, Isfahan, Hamadan, Zanjan, Kordestan, Lorestan and West Azarbayjan, and were tested for G protein gene of HRSV by RT-PCR. Of the 107 respiratory samples, 24 (22. 42٪) were positive for HRSV, of which 16 (66. 6٪) belonged to subgroup A and 8 (33. 4٪) to subgroup B. Phylogenetic analysis revealed that subgroup A strains fell in two genotypes GA1 and GA2, whereas subgroup B strains clustered in genotype BA. This study revealed that multiple genotypes of HRSV cocirculated during the season 2009 in Iran. Also subgroup A strains were more prevalent than subgroup B strains, and genotype GA1 was predominant during the season.

Cystic fibrosis (CF) is characterized by chronic pulmonary disease, insufficient pancreatic and digestive function, and abnormal sweat concentration. There is controversy about predisposing factors of nephrolithiasis and nephrocalcinosis in patients with cystic fibrosis. We assessed the results of metabolic evaluation in patients with cystic fibrosis and its correlation with nephrocalcinosis. Forty five CF patients, mean age 47.1 months, were enrolled in the study. No one had past history of nephrolithiasis and/or nephrocalcinosis. The records were reviewed for clinical characteristics and all patients underwent metabolic evaluation including serum electrolyte measurements and spot urine analysis. Ultrasonography was performed in all patients to detect nephrocalcinosis and urolithiasis. Nephrocalcinosis was found in 5 (11%) patients. No patient had clinical symptoms of nephrolithiasis and/or micro/macroscopic hematuria. Metabolic evaluation of the CF patients versus normal reference values showed decreased serum uric acid in 48.8%, elevated serum phosphate in 24.4%, and urine oxalate excretion in 51%. Metabolic evaluation of the nephrocalcinosis positive patients versus nephrocalcinosis negative group showed no statistical difference in serum electrolytes. The mean value of urine calcium excretion was lower in patients with nephrocalcinosis (P=0.001). Despite lack of any significant correlation, higher numerical hyperoxaluria was observed in patients with severe steatorrhea. There was no statistical correlation between steatorrhea and urine calcium as well as oxalate excretion. Hypocalciuria in the nephrocalcinotic CF patients may be seen. It can be hypothesized that hypocalciuria may be due to a primary defect in renal calcium metabolism in CF patients.

Successful results after one-stage trans-anal pull-through (OSTAPT) operation for Hirschsprung's disease (HD) depend on accurate identification of the aganglionic segment in intra-operative frozen section (FS). Misinterpretation of the findings of the rectal biopsy is an anxiety-evoking pitfall for the surgeon. This study aims to describe our experiences in comparing results of FS and permanent Section (PS) rectal biopsies in children with HD who were candidates for OSTAPT in a single-step operation. Subjects under the age of 14 years, admitted from March 2000 to July 2008 in a university-affiliated children's hospital for open rectal biopsy to diagnose HD were included in the study. All biopsies were taken 2-3 cm above the dentate line. 210 specimens of full-thickness rectal biopsy were obtained for both frozen section and permanent biopsy from all patients, examined by two well experienced pediatric pathologists for ascertaining the presence of ganglion cells, and the results were compared. Analysis was performed by SPSS Software version 11.5. Two-hundred one infants and children underwent FS rectal biopsy to exclude HD. Positive results were seen in 63.8% of the specimens examined as PS and in 58.3% of FS samples. 93.9% of positive results in FS studies were confirmed by PS studies. 6.1% of FS reports were false positive and 21.7% were false negative (P<0.001). The sensitivity of FS was 85.8% and specificity 90.2%. Positive predictive value (PPV) was 93.9% and negative predictive value (NPV) was 78.3% in FS studies (P<0.001). The accuracy of FS was 80.4%. Although FS of the rectal biopsy is useful in defining the aganglionic segment during operation, according to this study, it cannot be used as the sole base for performing primary pull-through operation before the results of the permanent section are on hand.

Hypothyroidism usually appears in the second decade of life and is thought to be associated with iron overload in patients with thalassemia major. This study aimed to evaluate thyroid dysfunctions in patients with beta-thalassemia major and to see if they appear in the earlier period of life. Thyroid function and iron load status were evaluated in 90 children with a mean age of 7.17±3.78 years with beta-thalassemia major by measuring serum free thyroxin (FT4), serum free triiodothyronine (FT3), total thyroxin (T3), serum total triiodothyronine (T4), thyroid-stimulating hormone (TSH) and ferritin levels from serum of patients admitted to the Pediatric Department, Faculty of Medicine University of Dicle between March 2005 and July 2009. A control group formed from an age-sex matched healthy children with a mean age of 6.98±3.66 years was also included. A standard thyrotropin releasing hormone test was applied to 3 patients who had high TSH levels and were classified as subclinical primer hypothyroidism. The study was designed according to the Declaration of Helsinki and informed consent was obtained from the parents of all participants. All thyroid parameters in patients were in the normal ranges compared with the controls except three of them which had high TSH levels. Serum ferritin level (2703±1649 ng/mL) in patients was significantly higher than in controls (81.5±15.5 ng/mL). The work implies that hypothyroidism could be even seen in the first decade of life in patients with beta-thalassemia major in spite of improved hematological cares.

Bacterial sepsis continues to be a major cause of morbidity and mortality in newborns. Bacterial pathogens of neonatal septicemia may vary from one country to another and within a country from one hospital or region to another. Both gram-negative and gram-positive bacteria are responsible in neonatal sepsis. This study was undertaken to determine the prevalent bacterial agents of neonatal sepsis and their antimicrobial susceptibility in a teaching hospital, Rasht, from February 2008 to February 2010. This prospective study includes 611 newborns admitted with the probable diagnosis of septicemia. We studied the cases with positive blood culture, the pathogens and antibiotic resistance to different antibiotics. Among 611 hospitalized newborns, 64 (10.6%) cases had positive blood culture. The commonest pathogens were Entrobacter (78.1%) and Klebsiella (6.2%). According to the results, low birth weight and prematurity were associated with higher risk of sepsis significantly. The most common pathogen was Enterobacter. Treatment with effective antibiotics (e.g. gentamicin, cost effective and easily available) and hygienic care in the neonatal unit are recommended to eliminate the infectious factors especially Entrobacter.

Growth charts are widely used to assess children's growth status and can provide a trajectory of growth during early important months of life. Racial differences necessitate using local growth charts. This study aimed to provide standardized growth curves of body mass index (BMI) for children living in northeast Iran. A total of 23730 apparently healthy boys and girls aged 25 to 60 months recruited for 20 days from those attending community clinics for routine health checks. Anthropometric measurements were done by trained health staff using WHO methodology. The LMSP method with maximum penalized likelihood, the Generalized Additive Models, the Box-Cox power exponential distribution distribution, Akaike Information Criteria and Generalized Akaike Criteria with penalty equal to 3 [GAIC(3)], and Worm plot and Q-tests as goodness of fit tests were used to construct the centile reference charts. The BMI centile curves for boys and girls aged 25 to 60 months were drawn utilizing a population of children living in northeast Iran. The results of the current study demonstrate the possibility of preparation of local growth charts and their importance in evaluating children's growth. Also their differences, relative to those prepared by global references, reflect the necessity of preparing local charts in future studies using longitudinal data.

Thalassemia is a common disease in many countries, in which several complications such as infections can occur. Although aberration in the function of the immune system could be a reason for such complication, a little is known about the status of humoral immune system in major beta thalassemia. In this study we measured serum immunoglobulins level in a group of patients with major beta thalassemia. Ninety nine patients with major beta thalassemia were enrolled in this study divided into two groups of splenctomized and not splenctomized patients. Serum IgG, IgM and IgA levels of these patients were measured and analyzed. Serum mean levels of IgG and IgM in patients of all ages in both groups were normal. The mean serum IgA level in the group of not splenectomized patients aged less than five years as well as in the splenectomized patients aged more than twenty years was increased. However, it was normal in other age groups. Although this study could not show any defect in the humoral immune system, evaluation of immunoglobulins could be useful to understand the relmarkable high rate of infection in the patients with major beta thalassemia.

It has been demonstrated that newborns feel pain completely. Thus, they should be treated with this in mind. Recent research showed that non-pharmacological interventions such as "Kangaroo Care" may be useful for decreasing pain in newborns. We tried to determine the effect of kangaroo care on the pain intensity of vaccination in healthy newborns. This study was a randomized case-control clinical trial. Subjects were 60 healthy full-term newborns delivered in a general Hospital, in Iran, from March to July 2006. They were randomly assigned to case and control groups. The case group received 30 minutes skin to skin contact, whereas infants in the control group were put, wrapped in a blanket, aside the mothers. Behavioral changes of newborns were evaluated and observed 2 minutes before, during, and 3 minutes after the intervention. All procedures were filmed. An assistant who was blinded to the study, scored behavior changes using Neonatal/Infant Pain Scale. Heart rate and oxygen saturation levels as displayed on the pulse monitor and duration of crying were recorded using a stopwatch. Mean pain intensity during the intervention v was significantly lower in the case group (P<0.006). Mean pain intensity 3 minutes after intervention was also significantly lower in the case group (P<0.021). Mean duration of crying was significantly lower in case group as well (P<0.001). Kangaroo care may be used to decrease pain intensity in newborns undergoing painful procedures.

Congenital heart disease (CHD) is the most common form of cardiovascular diseases in children. This study was performed from September 2006 to August 2007 in Ardebil, Westnorthern Iran. The aim was to determine the prevalence of heart murmur in newborns and its correlation with CHD. In a 1-year cross sectional descriptive-analytic study, 2928 newborns were screened for heart murmur during routine neonatal physical examination. All babies with murmur underwent echocardiography. Murmur was detected in 91 (3.1%) neonates, of whom 47 (51.6%) had a congenital heart disease. The most common (17.6%) abnormality was ventricular septal defect. Patent ductus arteriosus was found in 10 (11%) patients. Remarkable high (round 50 %) rate of CDH in newborns presenting with heart murmur, urges to observe these neonates closely to establish the diagnosis of congenital heart disease and early referral to pediatric cardiologist.

Acute hemorrhagic edema of infancy (AHEI) is a benign self limiting leukocytoclastic vasculitis in young children. Serious complications, e.g. renal and gastrointestinal involvement, are not usually detected in AHEI patients. We report five patients with AHEI. Our patients were 17 to 21 months old. One patient presented with gastrointestinal bleeding due to this syndrome, the other one experienced second attack and scrotal edema due to epididymo-orchitis, while the third patient had renal involvement as hematuria and the other one had bilateral auricular chondritis. One of our cases was a typical case of AHEI without any complications, so a skin biopsy was not necessary. In this study, we describe the symptoms, probable triggering factors and treatment of choice for each patient. Although AHEI is a childhood vasculitis with no impairment of the general condition, some organ involvements such as gastrointestinal, renal or scrotal lesions and rarely chondritis are probable in these patients.

Chorioangiomas are the most common benign tumors of the placenta originating from primitive angioblastic tissues. It comprises near 1 percent of placental tumors. Clinical manifestations in the newborn are rare and usually associated with tumors greater than 5 cm in diameter and consist of polyhydramnios, fetal anemia, massive edema with pleural effusion, ascites and intrauterine growth retardation. We present a case with large chorioangioma as the cause of non-immunologic hydrops fetalis with a successful outcome. The patient was a female newborn with history of polyhydramnios, symptoms of congestive heart failure and associated anemia, thrombocytopenia and coagulopathy. The pathophysiology and management of the complications of hydrops fetalis with chorioangioma are discussed Chorioangioma of the placenta has potentially serious perinatal risks and so the pregnancy needs to have regular surveillance. The chance of developing complications is directly related with the tumor size.

Diaphragmatic paralysis in newborns is related to brachial plexus palsy. It can cause respiratory failure necessitating prolonged mechanical ventilation and subsequent extubation failure. We present a two-hour-old male newborn with a birth weight of 4500 grams who had a right-sided brachial plexus palsy and right diaphragmatic paralysis due to shoulder dystocia. He developed respiratory distress due to isolated paralysis of the right hemi diaphragm. The clinical course was progressive, his condition worsening despite oxygen application. Physical examination, chest X-rays and M-mode ultrasonography of the diaphragm confirmed the diagnosis diaphragmatic paralysis. Surgical plication of diaphragm was done earlier than the usual time because of recurrent extubation failure. Diaphragmatic plication led to rapid improvement of pulmonary function and allowed discontinuation of mechanical ventilation in less than 3 days. Early diaphragmatic plication enhances weaning process and may prevent or minimize the morbidity associated with long-term mechanical ventilation in a neonate with diaphragmatic paralysis.

Several clinical entities combine ectodermal dysplasia (ED) and cleft lip and/or palate (CL/P). These disorders have been recognized with a narrow phenotypic spectrum and very similar clinical features. We report a case with a clinical diagnosis of Hay Wells syndrome (ankyloblepharon, ED and CL/P), who is a descendent of a mother with Bowen Armstrong syndrome (ED, CL/P, mental retardation). Due to the clinical similarities, we suggest that Hay Wells syndrome and Bowen Armstrong syndrome may be the same clinical entity with variable manifestations. This case highlights the difficulties in trying to classify the ED syndromes on clinical features.