Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic ... more Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic of Lok Nayak Hospital, Delhi were assessed in this study. Achondroplasia was the commonest (n=9) skeletal dysplasia; conclusive diagnosis was not possible in six children. Molecular confirmation of clinicoradiological phenotype was done in 18 of 40 cases. Genetic study of all achondroplasia cases revealed c. 1138 G>A, p. Gly380Arg mutation in hot spot.
Background: Hepatitis E is mainly an acute and self-limiting disease which is endemic to resource... more Background: Hepatitis E is mainly an acute and self-limiting disease which is endemic to resource poor regions of the world. Some patients have an increased susceptibility to develop fulminant hepatitis which is a rare disorder with high mortality and resource cost. In this study, a metabonomic approach was used to investigate the biochemical perturbation of the serum samples from acute liver failure patients induced by hepatitis E virus. Materials and Methods: Serum samples from hepatitis E virus-related acute liver failure patients (n = 20) and healthy controls (n = 20) were studied. Gas chromatography–mass spectrometry technique integrated with a commercial mass spectral library for the peak identification was used to detect the serum metabonome. Results: Out of the 24 metabolites detected, the serum levels of benzenepropanoic acid, lactic acid, hexadecanoic acid, L-proline, serine, and butanoic acid were significantly higher in the acute liver failure patients than those in the ...
sample volume [5]. Furthermore, the incorporation of TMS in NBS has revolutionized many aspects o... more sample volume [5]. Furthermore, the incorporation of TMS in NBS has revolutionized many aspects of the process beyond the most obvious of allowing for testing of many analytes on the same sample at the same time [6,7]. Homocystinuria is an inherited metabolic disorder resulting from a defect in the methionine (Met) metabolism usually characterized by an aberrant buildup of total homocysteine (tHCY) and its cognates such as HCY, HCY-cysteine complex, and others in blood and urine of the affected neonate. Clinical presentation for homocystinuria is often accompanied by symptoms such as mental retardation, thromboembolism, psychiatric disorders, ectopia lentis, and skeletal abnormalities [8-10]. However, the re-methylation disorder is often characterized by diverse clinical presentations such as developmental delay, seizure, hypotonia, microcephaly, feeding difficulty, neurological deterioration,
Pre analytical process of extraction for accurate detection of organic acids is a crucial step in... more Pre analytical process of extraction for accurate detection of organic acids is a crucial step in diagnosis of organic acidemias by GCMS analysis. This process is accomplished either by solid phase extraction (SPE) or by liquid-liquid extraction (LLE). Both extraction procedures are used in different metabolic laboratories all over the world. In this study we compared these two extraction procedures in respect of precision, accuracy, percent recovery of metabolites, number of metabolites isolated, time and cost in a resource constraint setup. We observed that the mean recovery from SPE was 84.1 % and by LLE it was 77.4 % (p value \0.05). Moreover, the average number of metabolites isolated by SPE and LLE was 161.8 ± 18.6 and 140.1 ± 20.4 respectively. The processing cost of LLE was economical. In a cost constraint setting using LLE may be the practical option if used for organic acid analysis.
Journal of clinical and diagnostic research : JCDR, 2014
Methyl Malonic Acid (MMA) is known to be an integral component of the cascade of events in mitoch... more Methyl Malonic Acid (MMA) is known to be an integral component of the cascade of events in mitochondrial energy metabolism and since heart failure involves energy pathways, it is probable that levels of MMA could be used as a reliable biomarker to objectively identify the disease during the early stages and help in prognostication. The present study was envisaged to evaluate the relation between urinary MMA levels in patients with Ischemic heart disease and in those progressing to failure. The relationship between the severity of the disease and the level of MMA in urine were also evaluated. Analysis of urinary MMA was done by Gas Chromatography-Mass Spectrometry (GC-MS) using stable isotope dilution. Twenty patients each with Ischemic Heart Disease, heart failure and controls were recruited in this pilot study. The mean value of MMA in patients with IHD was 126.71(±66.3) pmol/L and those with IHF was 390.76 (±97.99) pmol/L with the difference being statistically significant (p<0...
Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited meta... more Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p. Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p. A s n 3 9 2 G l u f s * 5) , c. 1 2 3 8 A >G (p. Ty r 4 1 3 C y s) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy. The original version of this chapter contained errors which have been corrected. These are detailed in the erratum to be found under 10.1007/8904_2015_448.
Human urine gives evidence of the metabolism in the body and contains numerous organic acids and ... more 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.
Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection... more Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD which has a poor correlation between hypertension and development of nephropathy, implying role of genetic factors or epigenetic factors. The knowledge regarding genetic factors is limited. Renalase is a novel hormone with its gene on chromosome 10, which secretes flavin adenine dinucleotide dependent amine oxidase. Renalase metabolizes circulating catecholamines and modulates blood pressure and cardiac function. Recently, two single nucleotide polymorphisms of renalase gene rs2576178 GG and rs2296545 CC have been linked to essential hypertension. The SNPrs2296545 CC is also shown to be associated with cardiac hypertrophy, dysfunction and ischemia. The association of these two single nucleotide polymorphisms with hypertensive nephrosclerosis has not been investigated. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD particularly hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). Results: Comparison shows that subjects with hypertensive nephrosclerosis had higher frequencies of rs2296545 C allele than the healthy controls (0.63 versus 0.47, p < 0.02). The odds ratio for rs2296545 CC genotype in hypertensive nephrosclerosis were 2.55 (95% CI, 1.03 to 6.42; p = 0.02) (CC versus GG) and 2.11 (95% CI, 1.01 to 4.42; p = 0.03) (CC versus CG + GG) compared to controls. Conclusion: These findings may provide novel insight into the role of additional genomic regions as susceptibility gene in the pathophysiology of hypertensive nephrosclerosis. Further, to account for geoethnic variation, studies on heterogeneous populations involving a larger sample size are required. The correlation between this structural change and actual levels of the enzyme or the activity are required to strengthen this association as well as to be clinically applicable.
Background: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for muco... more Background: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for mucopolysaccharidosis disease (MPS I and MPS II). Methods: Seventeen cases (6 MPS I and 11 MPS II) and sixty healthy controls were enrolled in study, conducted from September 2008 to December 2012. The mean ± SD age of MPS1 (n=6, 5 males) and MPS II was 7.02 ± 3.25 and 5.2 ± 2.15 years, respectively. Disease status was confirmed by clinical features and enzyme assay. Urinary glycosaminoglycans were measured in spot urine samples and expressed in relation to creatinine content. HCIIT measurement was done using sandwich ELISA at enrolment and after 12 and 24 months of recruitment. Results: Urinary glycosaminoglycans and HCIIT were elevated in all patients compared to their healthy controls. Both markers could not discriminate between the type of mucopolysaccharidosis. Conclusion: Heparin Cofactor II Thrombin Complex is a good biomarker for mucopolysaccharidosis I and II.
Autism Spectrum Disorder (ASD) is a clinically heterogenous condition with a wide range of etiolo... more Autism Spectrum Disorder (ASD) is a clinically heterogenous condition with a wide range of etiological factors and causing significant public health burden. ASD poses a serious developmental disadvantage to the child in the form of poor schooling, social function and adult productivity. Thus, framing evidence-based national guidelines is a pressing need. Process: The meeting on formulation of national consensus guidelines on neurodevelopmental disorders was organized by Indian Academy of Paediatrics in Mumbai on 18 th and 19 th December 2015. The invited experts included Pediatricians, Developmental Pediatricians, Psychiatrists, Remedial Educators, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. Thereafter, a committee was established to review the points discussed in the meeting. Objective: To provide consensus guidelines on evaluation and management of ASD in children in India. Recommendations: Intervention should begin as early as possible. A definitive diagnosis is not necessary for commencing intervention. Intervention should target core features of autism i.e. deficits in social communication and interaction, and restricted repetitive patterns of behavior, activities and/ or interests. Intervention should be specific, evidence-based, structured and appropriate to the developmental needs of the child. Management of children should be provided through interdisciplinary teams, coordinated by the Pediatrician. Management of co-morbidities is critical to effectiveness of treatment. Pharmacotherapy may be offered to children when there is a specific target symptom or co-morbid condition.
To evaluate the diagnostic accuracy of a set of predefined biomarkers (index test) in diagnosing ... more To evaluate the diagnostic accuracy of a set of predefined biomarkers (index test) in diagnosing diseases targeted in expanded newborn screening (ENS) namely organic acidemias, fatty acid oxidation disorders, and amino acid disorders. Methods: This was a prospective study. The study population consisted of out born neonates admitted to a teaching hospital for the study duration of 12 months. The presence of any of the predefined biomarkers was considered index test positive. Tandem Mass Spectrometry on dried blood samples along with urinary gas chromatography mass spectrometry (GCMS) was considered the gold standard (reference test) for diagnosis of diseases targeted in ENS. Results: A total of 783 out born neonates were evaluated using the index test and 30 tested positive, out of which, 18 were reference test positive. All index test negative neonates (n = 30) were reference test negative. The index test had a sensitivity of 100%, specificity of 71.42%, with 60% positive predictive value and 100% negative predictive value. The area under ROC curve for the index test was 80%. Conclusions: In the absence of universal screening programs, the evaluated biomarkers (index test) can be useful to decide which cases should be selectively referred for mass spectrometric techniques. Further multicentric studies are required to assess these biomarkers before incorporating them in national programs.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manif... more Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manifest after birth with ambiguous genitalia and salt-wasting crisis. However, genital ambiguity is not seen in male babies and may be mild in female babies, leading to a missed diagnosis of classical CAH at birth. In this review, we provide a standard operating protocol for routine newborn screening for CAH in Indian settings. A standardization of first tier screening tests with a single consistent set of cutoff values stratified by gestational age is also suggested. The protocol also recommends a two-tier protocol of initial immunoassay/time resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen positive babies, wherever feasible. Routine molecular and genetic testing is not essential for establishing the diagnosis in all screen positive babies, but has significant utility in prenatal diagnosis and genetic counseling for future pregnancy.
Justification Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage dis... more Justification Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinical manifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD has paucity of information and optimal management guidelines for Indian patients. Process Gaucher Disease Task Force was formed under the auspices of the Society for Indian Academy of Medical Genetics. Invited experts from various specialties formulated guidelines for the management of patients with GD. A writing committee was formed and the draft guidelines were circulated by email to all members for comments and inputs. The guidelines were finalized in December 2016 at the annual meeting of the Indian Academy of Medical Genetics. Objectives These guidelines are intended to serve as a standard framework for treating physicians and the health care systems for optimal management of Gaucher disease in India and to define...
Objective: To determine an appropriate cutoff of capillary Thyroid stimulating hormone (TSH) for ... more Objective: To determine an appropriate cutoff of capillary Thyroid stimulating hormone (TSH) for congenital hypothyroidism.
We describe a 10-year-old boy with X-linked ichthyosis, Kallmann Syndrome and unilateral renal ag... more We describe a 10-year-old boy with X-linked ichthyosis, Kallmann Syndrome and unilateral renal agenesis who presented with nephrotic syndrome. DNA analysis revealed deletion of the Steroid Sulfatase (STS) gene. STS deficiency in X-linked ichthyosis leads to cholesterol sulfate accumulation, which induces transglutaminase-1 dysfunction. Since the slit diaphragm of the glomerular epithelial cell is a modified adherens junction, the accumulation of cholesterol sulfate could interfere with the normal slit diaphragm function of the glomerular visceral epithelial cell, resulting in nephrotic range proteinuria. The child went into remission on oral prednisolone.
Early detection and prevention of birth defects is necessary to further reduce neonatal morbidity... more Early detection and prevention of birth defects is necessary to further reduce neonatal morbidity and mortality. A birth defect registry or surveillance system is necessary to assess the exact magnitude, profile and modifiable risk factors for birth defects. We review the existing efforts and suggest possible options for addressing this important issue. Connecting birth defects registry with the pre-existing programs such as National Neonatal Perinatal Database could be one of the option.
Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. Afte... more Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. After diagnosis, parents often express and wish that if it was possible to detect it during pregnancy and could it be avoided in the future pregnancy. This makes it essential that pediatricians should have some idea about the basic screening methods and strategy used during pregnancy.
CASE REPORTS amino acid change p.G566D and baby presented with typical manifestations of HLH. Ear... more CASE REPORTS amino acid change p.G566D and baby presented with typical manifestations of HLH. Early genetic testing is needed to confirm FHL as allogenic HCT is the only curative therapy. It further helps in testing of at risk relatives, carrier testing, genetic counseling and prenatal testing for pregnancies at risk if disease causing mutation in family are known. As in our case we did prenatal diagnosis for the second child which was negative for mutation in STXBP2 gene.
Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic ... more Forty cases with disproportionate short stature (median age 3.1 y; 24 males) from genetic clinic of Lok Nayak Hospital, Delhi were assessed in this study. Achondroplasia was the commonest (n=9) skeletal dysplasia; conclusive diagnosis was not possible in six children. Molecular confirmation of clinicoradiological phenotype was done in 18 of 40 cases. Genetic study of all achondroplasia cases revealed c. 1138 G>A, p. Gly380Arg mutation in hot spot.
Background: Hepatitis E is mainly an acute and self-limiting disease which is endemic to resource... more Background: Hepatitis E is mainly an acute and self-limiting disease which is endemic to resource poor regions of the world. Some patients have an increased susceptibility to develop fulminant hepatitis which is a rare disorder with high mortality and resource cost. In this study, a metabonomic approach was used to investigate the biochemical perturbation of the serum samples from acute liver failure patients induced by hepatitis E virus. Materials and Methods: Serum samples from hepatitis E virus-related acute liver failure patients (n = 20) and healthy controls (n = 20) were studied. Gas chromatography–mass spectrometry technique integrated with a commercial mass spectral library for the peak identification was used to detect the serum metabonome. Results: Out of the 24 metabolites detected, the serum levels of benzenepropanoic acid, lactic acid, hexadecanoic acid, L-proline, serine, and butanoic acid were significantly higher in the acute liver failure patients than those in the ...
sample volume [5]. Furthermore, the incorporation of TMS in NBS has revolutionized many aspects o... more sample volume [5]. Furthermore, the incorporation of TMS in NBS has revolutionized many aspects of the process beyond the most obvious of allowing for testing of many analytes on the same sample at the same time [6,7]. Homocystinuria is an inherited metabolic disorder resulting from a defect in the methionine (Met) metabolism usually characterized by an aberrant buildup of total homocysteine (tHCY) and its cognates such as HCY, HCY-cysteine complex, and others in blood and urine of the affected neonate. Clinical presentation for homocystinuria is often accompanied by symptoms such as mental retardation, thromboembolism, psychiatric disorders, ectopia lentis, and skeletal abnormalities [8-10]. However, the re-methylation disorder is often characterized by diverse clinical presentations such as developmental delay, seizure, hypotonia, microcephaly, feeding difficulty, neurological deterioration,
Pre analytical process of extraction for accurate detection of organic acids is a crucial step in... more Pre analytical process of extraction for accurate detection of organic acids is a crucial step in diagnosis of organic acidemias by GCMS analysis. This process is accomplished either by solid phase extraction (SPE) or by liquid-liquid extraction (LLE). Both extraction procedures are used in different metabolic laboratories all over the world. In this study we compared these two extraction procedures in respect of precision, accuracy, percent recovery of metabolites, number of metabolites isolated, time and cost in a resource constraint setup. We observed that the mean recovery from SPE was 84.1 % and by LLE it was 77.4 % (p value \0.05). Moreover, the average number of metabolites isolated by SPE and LLE was 161.8 ± 18.6 and 140.1 ± 20.4 respectively. The processing cost of LLE was economical. In a cost constraint setting using LLE may be the practical option if used for organic acid analysis.
Journal of clinical and diagnostic research : JCDR, 2014
Methyl Malonic Acid (MMA) is known to be an integral component of the cascade of events in mitoch... more Methyl Malonic Acid (MMA) is known to be an integral component of the cascade of events in mitochondrial energy metabolism and since heart failure involves energy pathways, it is probable that levels of MMA could be used as a reliable biomarker to objectively identify the disease during the early stages and help in prognostication. The present study was envisaged to evaluate the relation between urinary MMA levels in patients with Ischemic heart disease and in those progressing to failure. The relationship between the severity of the disease and the level of MMA in urine were also evaluated. Analysis of urinary MMA was done by Gas Chromatography-Mass Spectrometry (GC-MS) using stable isotope dilution. Twenty patients each with Ischemic Heart Disease, heart failure and controls were recruited in this pilot study. The mean value of MMA in patients with IHD was 126.71(±66.3) pmol/L and those with IHF was 390.76 (±97.99) pmol/L with the difference being statistically significant (p<0...
Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited meta... more Glutaric acidemia I (GA I, #231670) is one of the treatable, autosomal recessively inherited metabolic disorders. Macrocephaly, acute encephalitis-like crises, dystonia and characteristic frontotemporal atrophy are the hallmarks of this disease. In this communication, we present the clinical, biochemical and molecular profile of seventeen GA I patients from 15 unrelated families from India and report seven novel mutations in GCDH gene (c.281G>A (p.Arg94Gln), c.401A>G (p.Asp134Gly), c.662T>C (p. Leu221Pro), c.881G>C (p.Arg294Pro), c.1173dupG (p. A s n 3 9 2 G l u f s * 5) , c. 1 2 3 8 A >G (p. Ty r 4 1 3 C y s) and c.1241A>C (p.Glu414Ala)). Out of these, c.662T>C (p.Leu221Pro) in exon 8 and c.281G>A (p.Arg94Gln) allele in exon 4 were low excretor alleles, whereas c.1241A>C (p.Glu414Ala), c.1173dupG and c.1207C>T (p.His403Tyr) in exon 11 were high excretor alleles. We conclude that c.1204C>T (p.Arg402Trp) is probably the most common mutant allele. Exons 11 and 8 are the hot spot regions of GCDH gene in Indian patients with GA I. An early diagnosis and timely intervention can improve the underlying prognosis. Molecular confirmation is helpful in providing genetic counselling and prenatal diagnosis in subsequent pregnancy. The original version of this chapter contained errors which have been corrected. These are detailed in the erratum to be found under 10.1007/8904_2015_448.
Human urine gives evidence of the metabolism in the body and contains numerous organic acids and ... more 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.
Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection... more Introduction: Chronic kidney disease (CKD) is an important public health problem. Early detection and treatment is a key factor for prevention of its complications. Hypertensive nephrosclerosis is a subtype of CKD which has a poor correlation between hypertension and development of nephropathy, implying role of genetic factors or epigenetic factors. The knowledge regarding genetic factors is limited. Renalase is a novel hormone with its gene on chromosome 10, which secretes flavin adenine dinucleotide dependent amine oxidase. Renalase metabolizes circulating catecholamines and modulates blood pressure and cardiac function. Recently, two single nucleotide polymorphisms of renalase gene rs2576178 GG and rs2296545 CC have been linked to essential hypertension. The SNPrs2296545 CC is also shown to be associated with cardiac hypertrophy, dysfunction and ischemia. The association of these two single nucleotide polymorphisms with hypertensive nephrosclerosis has not been investigated. Methods: We designed a case-control study to investigate whether the two known renalase gene polymorphisms rs2576178 and rs2296545 are associated with CKD particularly hypertensive nephrosclerosis. We genotyped these two polymorphisms in 287 subjects from North Indian population (106 CKD cases and 181 controls). Results: Comparison shows that subjects with hypertensive nephrosclerosis had higher frequencies of rs2296545 C allele than the healthy controls (0.63 versus 0.47, p < 0.02). The odds ratio for rs2296545 CC genotype in hypertensive nephrosclerosis were 2.55 (95% CI, 1.03 to 6.42; p = 0.02) (CC versus GG) and 2.11 (95% CI, 1.01 to 4.42; p = 0.03) (CC versus CG + GG) compared to controls. Conclusion: These findings may provide novel insight into the role of additional genomic regions as susceptibility gene in the pathophysiology of hypertensive nephrosclerosis. Further, to account for geoethnic variation, studies on heterogeneous populations involving a larger sample size are required. The correlation between this structural change and actual levels of the enzyme or the activity are required to strengthen this association as well as to be clinically applicable.
Background: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for muco... more Background: Serum heparin cofactor II-thrombin complex (HCII-T) is an emerging biomarker for mucopolysaccharidosis disease (MPS I and MPS II). Methods: Seventeen cases (6 MPS I and 11 MPS II) and sixty healthy controls were enrolled in study, conducted from September 2008 to December 2012. The mean ± SD age of MPS1 (n=6, 5 males) and MPS II was 7.02 ± 3.25 and 5.2 ± 2.15 years, respectively. Disease status was confirmed by clinical features and enzyme assay. Urinary glycosaminoglycans were measured in spot urine samples and expressed in relation to creatinine content. HCIIT measurement was done using sandwich ELISA at enrolment and after 12 and 24 months of recruitment. Results: Urinary glycosaminoglycans and HCIIT were elevated in all patients compared to their healthy controls. Both markers could not discriminate between the type of mucopolysaccharidosis. Conclusion: Heparin Cofactor II Thrombin Complex is a good biomarker for mucopolysaccharidosis I and II.
Autism Spectrum Disorder (ASD) is a clinically heterogenous condition with a wide range of etiolo... more Autism Spectrum Disorder (ASD) is a clinically heterogenous condition with a wide range of etiological factors and causing significant public health burden. ASD poses a serious developmental disadvantage to the child in the form of poor schooling, social function and adult productivity. Thus, framing evidence-based national guidelines is a pressing need. Process: The meeting on formulation of national consensus guidelines on neurodevelopmental disorders was organized by Indian Academy of Paediatrics in Mumbai on 18 th and 19 th December 2015. The invited experts included Pediatricians, Developmental Pediatricians, Psychiatrists, Remedial Educators, Pediatric Neurologists and Clinical Psychologists. The participants framed guidelines after extensive discussions. Thereafter, a committee was established to review the points discussed in the meeting. Objective: To provide consensus guidelines on evaluation and management of ASD in children in India. Recommendations: Intervention should begin as early as possible. A definitive diagnosis is not necessary for commencing intervention. Intervention should target core features of autism i.e. deficits in social communication and interaction, and restricted repetitive patterns of behavior, activities and/ or interests. Intervention should be specific, evidence-based, structured and appropriate to the developmental needs of the child. Management of children should be provided through interdisciplinary teams, coordinated by the Pediatrician. Management of co-morbidities is critical to effectiveness of treatment. Pharmacotherapy may be offered to children when there is a specific target symptom or co-morbid condition.
To evaluate the diagnostic accuracy of a set of predefined biomarkers (index test) in diagnosing ... more To evaluate the diagnostic accuracy of a set of predefined biomarkers (index test) in diagnosing diseases targeted in expanded newborn screening (ENS) namely organic acidemias, fatty acid oxidation disorders, and amino acid disorders. Methods: This was a prospective study. The study population consisted of out born neonates admitted to a teaching hospital for the study duration of 12 months. The presence of any of the predefined biomarkers was considered index test positive. Tandem Mass Spectrometry on dried blood samples along with urinary gas chromatography mass spectrometry (GCMS) was considered the gold standard (reference test) for diagnosis of diseases targeted in ENS. Results: A total of 783 out born neonates were evaluated using the index test and 30 tested positive, out of which, 18 were reference test positive. All index test negative neonates (n = 30) were reference test negative. The index test had a sensitivity of 100%, specificity of 71.42%, with 60% positive predictive value and 100% negative predictive value. The area under ROC curve for the index test was 80%. Conclusions: In the absence of universal screening programs, the evaluated biomarkers (index test) can be useful to decide which cases should be selectively referred for mass spectrometric techniques. Further multicentric studies are required to assess these biomarkers before incorporating them in national programs.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manif... more Congenital adrenal hyperplasia (CAH) is an autosomal recessive endocrine disorder which can manifest after birth with ambiguous genitalia and salt-wasting crisis. However, genital ambiguity is not seen in male babies and may be mild in female babies, leading to a missed diagnosis of classical CAH at birth. In this review, we provide a standard operating protocol for routine newborn screening for CAH in Indian settings. A standardization of first tier screening tests with a single consistent set of cutoff values stratified by gestational age is also suggested. The protocol also recommends a two-tier protocol of initial immunoassay/time resolved fluoroimmunoassay followed by liquid chromatography tandem mass spectrometry for confirmation of screen positive babies, wherever feasible. Routine molecular and genetic testing is not essential for establishing the diagnosis in all screen positive babies, but has significant utility in prenatal diagnosis and genetic counseling for future pregnancy.
Justification Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage dis... more Justification Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinical manifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD has paucity of information and optimal management guidelines for Indian patients. Process Gaucher Disease Task Force was formed under the auspices of the Society for Indian Academy of Medical Genetics. Invited experts from various specialties formulated guidelines for the management of patients with GD. A writing committee was formed and the draft guidelines were circulated by email to all members for comments and inputs. The guidelines were finalized in December 2016 at the annual meeting of the Indian Academy of Medical Genetics. Objectives These guidelines are intended to serve as a standard framework for treating physicians and the health care systems for optimal management of Gaucher disease in India and to define...
Objective: To determine an appropriate cutoff of capillary Thyroid stimulating hormone (TSH) for ... more Objective: To determine an appropriate cutoff of capillary Thyroid stimulating hormone (TSH) for congenital hypothyroidism.
We describe a 10-year-old boy with X-linked ichthyosis, Kallmann Syndrome and unilateral renal ag... more We describe a 10-year-old boy with X-linked ichthyosis, Kallmann Syndrome and unilateral renal agenesis who presented with nephrotic syndrome. DNA analysis revealed deletion of the Steroid Sulfatase (STS) gene. STS deficiency in X-linked ichthyosis leads to cholesterol sulfate accumulation, which induces transglutaminase-1 dysfunction. Since the slit diaphragm of the glomerular epithelial cell is a modified adherens junction, the accumulation of cholesterol sulfate could interfere with the normal slit diaphragm function of the glomerular visceral epithelial cell, resulting in nephrotic range proteinuria. The child went into remission on oral prednisolone.
Early detection and prevention of birth defects is necessary to further reduce neonatal morbidity... more Early detection and prevention of birth defects is necessary to further reduce neonatal morbidity and mortality. A birth defect registry or surveillance system is necessary to assess the exact magnitude, profile and modifiable risk factors for birth defects. We review the existing efforts and suggest possible options for addressing this important issue. Connecting birth defects registry with the pre-existing programs such as National Neonatal Perinatal Database could be one of the option.
Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. Afte... more Pediatricians are the first contact of a child with genetic disorders such as Down Syndrome. After diagnosis, parents often express and wish that if it was possible to detect it during pregnancy and could it be avoided in the future pregnancy. This makes it essential that pediatricians should have some idea about the basic screening methods and strategy used during pregnancy.
CASE REPORTS amino acid change p.G566D and baby presented with typical manifestations of HLH. Ear... more CASE REPORTS amino acid change p.G566D and baby presented with typical manifestations of HLH. Early genetic testing is needed to confirm FHL as allogenic HCT is the only curative therapy. It further helps in testing of at risk relatives, carrier testing, genetic counseling and prenatal testing for pregnancies at risk if disease causing mutation in family are known. As in our case we did prenatal diagnosis for the second child which was negative for mutation in STXBP2 gene.
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Papers by Seema Kapoor