Human urine gives evidence of the metabolism in the body and contains numerous organic acids and other compounds at a variety of concentration. The concentration of organic acids in urine varies from population to population due to genotype, food habits and other epigenetic and environmental influences. Knowledge of the reference values for urinary organic acids in a healthy pediatric population is very important for critical evaluation. This study was designed to quantify 16 organic acids in a healthy north Indian pediatric population. Early morning urine samples from healthy pediatric subjects of age 1 day to 16 years who did not have symptoms of any disease were analyzed for organic acid content. The children were not on any supplemental vitamins or drugs and were on a free and unrestricted diet. The creatinine concentration of each sample was determined before organic acid analysis. Organic acids were extracted from urine with ethyl acetate, extracted residue was air dried, converted into trimethylsilyl derivatives and analysed by gas chromatography mass spectrometry. Here we reported the age wise mean values and standard deviations for each compound, adjusted for creatinine content (mmol/mol of creatinine). We found the concentration of most of the metabolites are higher in our population in comparison to other populations. Such data may help to provide a basis for diagnosing metabolic abnormalities in patients in a specific ethnicity.

It is possible to ascertain the diagnosis in most of the cases of intellectual disability using a judicious and sequential battery of tests.

The year 2013 marks 50 years of both newborn screening and the Indian Academy of Pediatrics. India has seen a lot of change in terms of motivation, evolution and implementation of newborn screening as pilot projects for few disorders. Facilities for implementing screening using tandem mass spectrometry or what is termed as expanded newborn screening have also become available. We attempt to discuss the evolution of newborn screening and the way to carry it forward in the country. The current strengths, the major obstacles and gritty challenges are enlisted. No moment could be so opportune than this year to discuss the rainbow of hope with all its colors with respect to newborn screening in our country.

Background: Interleukin-18 (IL-18) is a pro inflammatory cytokine which plays a key role in the acute and chronic inflammatory phases of Rheumatoid Arthritis (RA). The Single Nucleotide Polymorphisms (SNPs) of IL-18 gene promoter region at positions -137 and -607, are postulated to be associated with RA. To test this, this study aimed to identify the association between these SNPs of the IL-18 gene promoter region of RA in south Indian patients. Materials and Methods:This study was carried on 190 subjects among which 90 were RA patients and 100 were age and sex matched controls. Genomic DNA was extracted by Salting out method. IL 18 gene promotor region SNPs, IL 18 -607 and IL 18 -137 were amplified by using sequence specific primers. The amplified products of different samples were separated by using a 1.5% agarose gel, stained with ethidium bromide and photographed. All statistical analyses were carried out by using SYSTAT 12 software.Results: At position 607, the frequencies of C allele, CC genotype, A allele and AA genotype were found to be significantly higher in patients and controls respectively and there was no significant difference in CA genotype. At position 137, there was no significant difference between the two groups with regard to G and C allelles but there was a significant increase in GG genotype of patients and CC genotype of controls. There was no association between duration of morning stiffness, rheumatoid factor positivity or negativity, age of onset and gender with distribution of genotypes and alleles.

We report an unusual combination of features comprising delayed tooth eruption and closure of the anterior fontanel as the sole presenting features in a child with cleidocranial dysplasia (CCD). Radiological survey revealed the presence of wormian bones in the skull, pseudoepiphysis at the base of the bilateral second metacarpal, and midline ossification defects at pubic symphysis in the presence of essentially normal clavicles. DNA sequencing of the RUNX2 gene detected a novel nonsense mutation in exon1 (c.166C>T; p.Q56X) in its glutamine-alanine (Q/A) repeat domain. The genotypes of all published cases of CCD with normal clavicles were reviewed. Additional dental and otolaryngological features were enlisted. Three cases with a milder dental phenotype and normal clavicles were associated with a mutation in the Q/A domain. Collectively, we found a novel CCD-causing nonsense mutation p.Q56X in the Q/A domain of the RUNX2 gene.

Autosomal dominant cerebellar ataxia type I is a heterogeneous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (~320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.

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AIMS AND OBJECTIVE:Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome.DESIGN:This was a case–control study.MATERIAL AND METHODSFifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene.RESULTS:The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535.CONCLUSION:Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.