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Background Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. Objective The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. Methods BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. Results BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3'-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. Conclusions BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.

Background Pediatric urolithiasis is a perplexing problem faced by pediatricians as well as urologists across the globe. By early diagnosis and treatment of these risk factors, future stone formation may be prevented. Aim: To evaluate the clinical, biochemical and metabolic characteristics of the patients and the interventions required to prevent recurrence. Methods: In this retrospective study, cohort of pediatric patients presenting with urolithiasis at Kasturba Medical College, Manipal formed the study population. Patient’s records served as study tools. Medical records department was approached and data was collected. Metabolic evaluation was done in all children. Urine tests included urinalysis, urine culture, 24 hours urinary pH, volume, calcium, oxalate, citrate, uric acid, and creatinine. Finally a total of 58 pediatric urolithiasis cases were included in this study. Results: Mean age of study subjects was 6.85±1.27 years. Top three presentations of pediatric urolithiasis were symptoms of Urinary tract infection (UTI), abdominal pain and flank pain in 29.3%, 24.1% and 17.2% children respectively. Gross hematuria was observed in 15.5% of cases. 82.6% of stones were renal stones. Calcium oxalate stone was most common (50%) variety found. Hyperoxaluria was the most common (79.3%) metabolic abnormality detected. 31% had stone recurrence during follow up and 8 of these had >1 metabolic abnormality. Only 6/28 (21.4%) patients managed conservatively had stone recurrence whereas 12/30 (40%) managed with a procedure had stone recurrence. Conclusions: Metabolic evaluation for urolithiasis helps us to identify children those at increased risk for recurrent stone disease. Thus metabolic evaluation is a must in all pediatric patients as it helps in segregating patients needing medical therapy.

Inborn errors of metabolism (IEM) lead to the physical and mental disability and death of infants, which can be prevented if treated early. Hence it is imperative in diagnosing these disorders at the earliest. The study is planned to differentiate suspected IEM by quantifying the lactate-pyruvate ratio (L/P ratio), Amino acid profiling by HPLC in addition to blood ammonia using the basic methodology in comparison to globally accepted mass spectroscopy technique and specific enzyme activity assays. The objective of this study is not to compete with the existing gold standard methodology rather makes the best of basic diagnostic modalities available. Five cases out of 100 referred cases of IEM suspicion showed the altered pattern of Aminogram correlating with high L/P ratio and Hyperammonemia, which were positive cases, as confirmed by the clinician who referred. Hence study parameters could be used as preliminary protocol to investigate and screen the IEM.

To study the etiology and clinical profile of congenital obstructive uropathy in children, renal status and growth at diagnosis and at follow-up and to determine the predictors for development of chronic kidney disease (CKD). An observational (retrospective-prospective) study was conducted at a tertiary care hospital in South India from September 2014 through September 2016. Sixty children diagnosed to have congenital obstructive uropathy with a minimum follow-up period of 5 y were included and followed up prospectively for 2 more years during the study period. The data of the children at admission and follow-up was obtained from the medical records and analyzed. Congenital uretero-pelvic junction obstruction followed by Posterior urethral valve were the most common etiologies identified. Male preponderance (88.3%) was observed with poor urinary stream being the most common presentation (36.6%). Forty percent of the population had elevated creatinine. Fifteen percent were hypertensive and 25% had growth failure at diagnosis. However, there was a reduction in the number of children with poor estimated glomerular filtration rate (eGFR), hypertension and growth faltering during follow-up. Among the risk factors, hypertension at diagnosis [O.R-12.8 (2.21–74.22) and p value

We report a case of eight-month-old breastfed male infant presented with developmental delay and knuckle pigmentation. Peripheral smear examination showed microcytic hypochromic anaemia. Knuckle pigmentation has given a clue for vitamin B12 deficiency and got confirmed by detailed biochemical investigations. On examination mother was found to be vitamin B12 deficient who also presented with knuckle pigmentation. Subsequently the infant was administered oral vitamin B12 and responded to the therapy as indicated by weight gain, improvement in development, normalisation of serum B12 and blood haemoglobin level.

Pyroglutamic aciduria is a condition usually associated with metabolic acidosis and increased excretion of pyroglutamic acid in urine. It occurs due to metabolic defect in γ-glutamyl cycle. Here we report a case of 5-month-old male baby presented with respiratory symptoms who had a history of two months age sibling death due to pyroglutamic aciduria which was diagnosed by Gas Chromatography Mass Spectrometry (GCMS). Analysis of urine for organic acid by GCMS in the present baby also showed increased excretion of pyroglutamic acid. Hence in the present baby history of sibling death due to pyroglutamic aciduria led to the early diagnosis. Proper medication and timely management during fever and cold resulted in normal development.

Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an eff ect of 5,10-methylenetetrahydrofolate reductase gene ( MTHFR ) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case – control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignifi cant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of nonsynonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3 ’ untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3 ’ UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the signifi cant role of MTHFR in ALL development.

Introduction. Primary thrombocytosis is very rare in children; reactive thrombocytosis is frequently observed in children with infections, anemia, and many other causes. Aims and Objectives. To identify the etiology of thrombocytosis in children and to analyze platelet indices (MPV, PDW, and PCT) in children with thrombocytosis. Study Design. A prospective observational study. Material and Methods. A total of 1000 patients with thrombocytosis (platelet > 400×109/L) were studied over a period of 2 years. Platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit (PCT) were noted. Results. Of 1000 patients, 99.8% had secondary thrombocytosis and only two children had primary thrombocytosis (chronic myeloid leukemia and acute myelogenous leukemia, M7). The majority of the children belonged to the age group of 1month to 2 years (39.7%) and male to female ratio was 1.6 : 1. Infection with anemia (48.3%) was the most common cause of secondary thrombocytosis followed by iron deficiency alone (17.2%) and infection alone (16.2%). Respiratory infection (28.3%) was the predominant infectious cause observed. Thrombocytosis was commonly associated with IDA among all causes of anemia and severity of thrombocytosis increased with severity of anemia (P=0.021). With increasing platelet count, there was a decrease in MPV (Conclusions. Primary thrombocytosis is extremely rare in children than secondary thrombocytosis. Infections in association with anemia are most commonly associated with reactive thrombocytosis and severity of thrombocytosis increases with severity of anemia.

Background: Extensive studies are conducted on heart, liver and endocrine abnormalities in thalassemia owing to their direct effect on survival, however, lung dysfunction has never been focused upon and is one of the least understood complications in β thalassemia. There’s a vacuum for data on pulmonary function tests in β thalassemia major in literature from India. Authors aimed to study pulmonary function and type of abnormality in cases with β thalassemia major above the age of 8yrs and to correlate the result with age and serum ferritin levels.Methods: Demographic data, hemoglobin value, serum ferritin levels, chelation details and transfusion requirement were analyzed. Spirometry was performed using COSMED pulmonary function test (PFT).Results: Among the 34 subjects studied, 21 were boys, and 13 were girls. Mean serum ferritin levels of the group was 3610.82±2679.51ng/mL and did not show a significant correlation with age, years of transfusion, and years of chelation. Forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) % values were lower in boys when compared to girls. PFT showed a restrictive pattern in the study group (FEV1/FVC=>0.7) with significant involvement in 73.5% of cases (FEV1

Introduction: Inborn errors of metabolism (IEM) are a group of disorders due to deficiency of the enzyme. The symptoms are due to the accumulation of toxic substances or deficiency of products. Organic aciduria is a group of IEM which is due to errors in the metabolism of branched chain amino acids and lysine. Studies showed that methylmalonicaciduria (MMA), glutaric aciduria, branched chain aminoacidurias are more common organicaciduria. Many methods are used for detection of methylmalonic acid some of them are not affordable by developing countries. Objective: To study the role of thin layer chromatography in detection of methylmalonic aciduria in children with suspected inborn errors of metabolism. Method: Untimed urine samples were collected from 385 children with clinically suspected inborn errors of metabolism and analyzed for MMA by colour reaction and thin layer chromatography (TLC). Bromocresol green and Ortho dianisidine were the dye used for spotting MMA on TLC. Result: Among 385 children who presented with developmental delay, seizures, hypotonia were worked up for underlying inborn errors of metabolism. Of them 52 children showed positive result for MMA by thin layer chromatography. Discussion: Significant number of children showed positive result for MMA by thin layer chromatography hence the method may be useful for screening methylmalonicaciduria. Further studies required to confirm the diagnosis

To highlight the varied clinical manifestations and management of idiopathic hypereosinophilic syndrome, a rare disorder in children. Retrospective review of case records of 3 patients who were diagnosed to have idiopathic hypereosinophilic syndrome (IHES) in a tertiary referral centre between 1997 and 2010 was performed. These 3 children presented with different symptoms and the first case had cardiac involvement. All had very high absolute eosinophil count (cells/mm3) 43,206, 9,082, 2,925, respectively. Diagnosis was confirmed by bone marrow biopsy in all three cases and supported by liver biopsy in the first two cases and inguinal lymphnode biopsy in the last case. All 3 children responded to treatment with steroids, with only second patient requiring hydroxyurea to control disease. Case 1 and 2 are on follow up for 13 y and 10 y respectively and both are asymptomatic. Case 3 expired due to sepsis 1 mo after diagnosis. Treatment with steroids with or without hydroxyurea gave good response in all 3 cases. Hence, they still remain the gold standard for the treatment of IHES in children.

To determine the composition of non pathogenic microflora (NPM) and pathogenic microflora (PM) and the assessment of factors affecting their colonization in the oropharynx. Oropharyngeal swabs were obtained from 464 infants, aged 15 days to I year, with or without clinical signs and symptoms of upper respiratory tract infection (URTI), for the current study.Culture was done on blood and chocolate agar, and the colonies were identified using standard microbiological procedures. The influence of age, presence of siblings and feeding patterns on colonization of oropharynx and the profile of NPM and PM in symptomatic and asymptomatic infants was studied. Colonization of oropharynx by NPM decreased with age whereas by PM increased with age significantly. Isolation of PM significantly increased in cases having siblings less than 18 years of age at home. Season showed a significant influence on the colonization of microflora in the oropharynx. Colonization by NPM was significantly higher in exclusively breast fed (EBF) infants, whereas by PM was higher in mixed fed (MF) infants. Symptomatic infants were higher in the MF group than in EBF group. Certain species of NPM exhibited significant inhibitory effects on colonization of PM. Assessment of the factors influencing the oropharyngeal colonization of microflora in infants identifies the risk factors for various infections in later life.

Primary amoebic meningo-encephalitis (PAM) is extremely rare and is caused by Naegleria fowleri. It is ?commonly seen in older children who swim in water contaminated with Naegleria species. It is very rare to contract the illness by any other means. We report a case of PAM in an infant aged 6 months. To the best of our knowledge, only one other case of PAM in an infant has been reported from India. A high index of suspicion is required in infants who manifest similarly to pyogenic meningitis but whose CSF shows no bacterial organisms so that a wet mount of a CSF sample can be done for early detection of Naegleria fowleri infection and appropriate intervention.

Establishing genetic basis of Idiopathic generalized epilepsies (IGE) is challenging because of their complex inheritance pattern and genetic heterogeneity. Kir4.1 inwardly rectifying channel (KCNJ10) is one of the independent genes reported to be associated with seizure susceptibility. In the current study we have performed a comprehensive in silico analysis of genetic variants in KCNJ10 gene at functional and structural level along with a case-control analysis for the association of rs1130183 (R271C) polymorphism in Indian patients with IGE. Age and sex matched 108 epileptic patients and normal healthy controls were examined. Genotyping of KCNJ10rs1130183 variation was performed using PCR-RFLP method. The risk association was determined by using odds ratio and 95% confidence interval. Functional effects of non-synonymous SNPs (nsSNPs) in KCNJ10 gene were analyzed using SIFT PolyPhen-2, I-Mutant 2.0, PANTHER and FASTSNP. Subsequently, homology modeling of protein three dimensional (3D) structures was performed using Modeller tool (9.10v) and compared the native protein with mutant for assessment of structure and stability. SIFT, PolyPhen-2, I-Mutant 2.0 and PANTHER collectively showed rs1130183, rs1130182 and rs137853073 SNPs inKCNJ10 gene affect protein structure and function. There was a considerable variation in the Root Mean Square Deviation (RMSD) value between the native and mutant structure (1.17Ǻ). Association analysis indicate KCNJ10rs1130183 did not contribute to risk of seizure susceptibility in Indian patients with IGE (OR- 0.38; 95%CI, 0.07-2.05) and T allele frequency (0.02%) was in concordance with dbSNP reports. This study identifies potential SNPs that may contribute to seizure susceptibility and further studies with the selected SNPs in larger number of samples and their functional analysis is required for understanding the variants of KCNJ10 with seizure susceptibility.

Case records of 68 newborns who required assisted ventilation over a 24 month period were reviewed. Fortyfour (64.7%) received intermittent mandatory ventilation, 10 (14.7%) received nasal CPAP and the remaining 14 (20.58%) received a combination of the above. Some of the indications for ventilation were infections (21), hyaline membrane disease (16), problems related to asphyxia (11), apnea of prematurity (10) and persistent pulmonary hypertension of newborn (5). The overall survival rate was 41.17%. In the CPAP group 90% (9/10) survived, while in the remaining survival was 32.7% (19/58). The best outcome was observed in persistent pulmonary hypertension of newborn (80%) followed by apnea of prematurity (70%) and hyaline membrane disease (43.75). Outcome was poor in conditions related to birth asphyxia (27.2%) and infections (19.05%). Survival rates were higher (44.4%) in babies weighing >1500g at birth as compared to 40.9% in babies

The transmembrane P-glycoprotein that functions as a drug-efflux transporter coded by ATP-binding cassette, subfamily B, member 1/Multidrug Resistance 1 (ABCB1/MDR1) gene is considered relevant to drug absorption and elimination, with access to the central nervous system. Effects of three ABCB1 single nucleotide polymorphisms (SNPs) in genotypic and haplotypic combination have been evaluated in a south Indian population for risk of pediatric medically refractory epilepsy. The study included age and sex matched medically refractory (N=113) cases and drug responsive epilepsy patients (N=129) as controls, belonging to the same ethnic population recruited from a tertiary referral centre, of Karnataka, Southern India. The genotype frequencies of SNPs c.1236C>T, c.2677G>T/A, and c.3435C>T were determined from genomic DNA of the cases and controls by PCR- RFLP and confirmatory DNA sequencing. 256 normal population samples of the same ethnicity were genotyped for the three loci to check for population stratification. Results indicate that there was no statistically significant difference between allele and genotype frequencies of refractory and drug responsive epilepsy patients. The predicted haplotype frequencies of the three polymorphisms did not show significant difference between cases and controls. The results confirm earlier observations on absence of association of ABCB1 polymorphisms with medically refractory epilepsy.

Background: Oxidative damage by free radicals has been implicated in kidney injury, especially in nephrotic syndrome (NS). Such a stress would influence the response of nephrotic children to therapy. Methods: The present study enrolled children with NS in active disease state and in remission and 50 healthy volunteers. Plasma protein thiol levels and ferric-reducing/antioxidant power were estimated spectrophotometrically in controls and in patients. Serum protein and albumin as well as urine protein were also estimated. Results: There was a significant decrease in plasma protein thiol levels in children with active disease when compared to controls as well as to subjects in remission. Ferric-reducing/antioxidant power values were significantly increased in NS and remained high in remission when compared to controls. Serum total protein and albumin were significantly decreased in nephrotics compared to controls. Further, a prospective study between the relapse and remission groups indicated a significant increase in plasma protein thiols in remission when compared to relapse exhibiting a positive response to treatment. Conclusion: A considerable alteration in the antioxidant status in NS indicates the pro-oxidant milieu existing in this condition which may have implications in the response to treatment of these patients.

Varicella is common and highly contagious and affects nearly all susceptible children before adolescence. Progressive varicella syndrome is a severe complication of primary Varicella Zoster Virus (VZV) infection, with visceral organ involvement, coagulopathy, severe hemorrhage, and continued vesicular lesion development. We report a rare case of progressive varicella syndrome with varicella gangrenosa in a previously well female child of ten months. She presented with history of recurrent vesiculo-bullous skin lesions involving the chest, back and extremities since two months with dry gangrene of 1st, 3rd and right great toe. VZV Polymerase Chain Reaction (PCR) of vesicle fluid was positive. Workup for immunodeficiency state was negative. She responded dramatically to intravenous acyclovir..

We report a variant of mirror hand in a 3.5-year-old boy who presented with multiple fingers. The x-ray revealed an attempt at fusion of 2 hypoplastic radii, 1 ulna, and multiple fingers. The unique feature of this case is a broad radius with proximal notching suggesting failed incomplete duplication. The reasons for this duplication and duplication of the fingers appear to be different.

Occasionally, insect bites producing systemic complications are the reason for admission to paediatric intensive care. We report an interesting case of multiple bee stings in a 2-year-old boy. The boy, who was stung more than 200 times by honey bees, had a severely deranged coagulation profile with marked elevation of the hepatic enzymes. This complication has not been reported to date. Prompt intensive supportive care led to the child's total recovery. Language: en

Seventy-eight parturient mothers undergoing elective caesarean section were studied with regard to the immediate neonatal outcome in those receiving general and spinal anesthesia. All mothers were of grade I anesthesia risk, were term and had singleton appropriate for gestational age babies. There was no difference in fetal acid base chemistry in the two groups. Babies delivered after general anesthesia appeared relatively depressed requiring more free flow oxygen and bag and mask ventilation though one minute Apgar scores showed no significant difference in either group. Induction delivery intervals were longer in the spinal group but it was not associated with more morbidity. Uterine incision delivery intervals were very small in both groups and no meaningful conclusion could be drawn as regards effect on the newborn. A plea is made for more frequent use of spinal anesthesia considering its many postnatal advantages.

Seventy eight parturient mothers undergoing elective caesarean section were studied with regard to the immediate neonatal outcome in those receiving general and spinal anesthesia. All mothers were of grade I anesthesia risk, were term and had singleton appropriate for gestational age fetuses. There was no difference in fetal acid base chemistry in the two groups. Babies delivered after general anesthesia appeared relatively depressed requiring more free flow oxygen and bag and mask ventilation, though one minute Apgar scores showed no significant difference in either group. Induction delivery intervals were longer in the spinal group but it was not associated with more morbidity. Uterine incision delivery intervals were very small in both groups and no meaningful conclusion could be drawn as regards effect on the newborn. A plea is made for more frequent use of spinal anesthesia considering its many postnatal advantages.

SummaryA 3-week-old baby with neonatally acquired tuberculous bronchopneumonia is presented. The diagnosis was considered because the neonate did not respond to conventional management of bronchopneumonia. The importance of including tuberculosis as a differential diagnosis in respiratory disorders, especially in developing countries, is emphasized.

Background: Infection remains an important complication in children with nephrotic syndrome. Besides being the commonest cause of mortalty, infections result in significant morbidity and may also be responsible for a poor response to steroid therapy or induce relapse in a child who has already attained remission. The study was undertaken to observe the type of infection in children with nephrotic syndrome and to study the relation of infection to relapse.

Serum apolipoproteins A (Apo-A) and B (Apo-B) and lecithin: cholesterol acyl transferase (LCAT) activities and 24-hour urinary cholesterol levels were estimated in 25 nephrotic children before and during steroid treatment with 4 weeks of daily prednisolone followed by another 4 weeks of alternate-day prednisolone. The patients with untreated nephrotic syndrome (NS) showed significant decrease in serum Apo-A and LCAT activities associated with significant increase in serum Apo-B and urinary cholesterol levels compared to healthy controls (n = 25). Serum Apo-A levels correlated directly and Apo-B levels inversely with the serum albumin concentrations. After a transient elevation, the serum Apo-A level returned to control range by 8 weeks of treatment accompanied by a gradual increase in serum LCAT activity and decrease in urinary cholesterol excretion. Though, the serum Apo-B level was decreased with treatment, it was still significantly high compared to the controls.

blood and Streptococcus pyogenes in pleural fluid. Treatment consisted of: antibiotics only, n = 3 (7.9%); chest drain only, n = 5 (13.2%); chest drain with fibrinolytics, n = 14 (36.8%); primary video-assisted thoracoscopic surgery, n = 16 (42.1%). Conclusion: Identification by culture positive organisms alone suggest Streptococcus pyogenes and Streptococcus pneumoniae are the leading causes of childhood empyema in Australia. There is a wide discrepancy in treatment approaches. The next step, while continuing to recruit subjects, is to use molecular techniques to identify and type bacteria in culture positive and negative pleural fluid. Funding: Supported by an unrestricted grant from GlaxoSmithKline, Belgium.