Madhulika Kabra

All India Institute of Medical Sciences, New Dilli, NCT, India

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Publications (248)519.69 Total impact

  • Indian journal of pediatrics. 02/2015;
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    ABSTRACT: Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding "common mutations" in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much delay in diagnosis with consequent harm to the patient.We report mutations in the ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal community. Six patients from the Agarwal community and two non-Agarwal patients harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous), in the ALDOB gene. Haplotyping performed in families confirmed a founder effect. The community has been known to harbor founder mutations in other genes such as the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder effect in the community in case of HFI. This may pave the path for a simpler and quicker test at least for this community in India. In addition to the founder mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A, c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the cohort from India.
    JIMD reports. 01/2015;
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    ABSTRACT: Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder characterized by cutaneous and ocular photosensitivity and an increased risk of developing cutaneous neoplasms. Progressive neurological abnormalities develop in a quarter of XP patients. To study the clinical profile and perform a mutation analysis in Indian patients with xeroderma pigmentosum. Ten families with 13 patients with XP were referred to our clinic over 2 years. The genes XPA, XPB and XPC were sequentially analyzed till a pathogenic mutation was identified. Homozygous mutations in the XPA gene were seen in patients with moderate to severe mental retardation (6/10 families) but not in those without neurological features. Two unrelated families with a common family name and belonging to the same community from Maharashtra were found to have an identical mutation in the XPA gene, namely c.335_338delTTATinsCATAAGAAA (p.F112SfsX2). Testing of the XPC gene in two families with four affected children led to the identification of the novel mutations c.1243C>T or p.R415X and c.1677C>A or p.Y559X. In two families, mutations could not be identified in XPA, XPB and XPC genes. The sample size is small. Indian patients who have neurological abnormalities associated with XP should be screened for mutations in the XPA gene.
    Indian journal of dermatology, venereology and leprology. 01/2015; 81(1):16-22.
  • Seema Kapoor, Sangeeta Gupta, Madhulika Kabra
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    ABSTRACT: 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.
    Indian pediatrics. 12/2014; 51(12):959-62.
  • Genetics in medicine: official journal of the American College of Medical Genetics 10/2014; 17(1). · 3.92 Impact Factor
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    ABSTRACT: Mucopolysaccharidosis IV A (Morquio syndrome A, MPS IVA) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfatase (GALNS). The mutation spectrum in this condition is yet to be determined in Indians. We aimed to analyze the mutations in the GALNS gene in Asian Indians with MPS IVA. All the exons and the adjacent intronic regions of the gene were amplified and sequenced in sixty-eight unrelated Indian families. We identified 136 mutant alleles comprising of 40 different mutations. We report twenty-two novel mutations that comprise of seventeen missense (p.Asn32Thr, p.Leu36Arg, p.Pro52Leu, p.Pro77Ser, p.Cys79Arg, p.His142Pro, p.Tyr191Asp, p.Asn204Thr, p.Gly188Ser, p.Phe216Ser, p.Trp230Cys, p.Ala291Ser, p.Gly317Arg, p.His329Pro, p.Arg386Ser, p.Glu450Gly, p.Cys501Ser), three splice-site variants (c.120 + 1G > C, c.1003-3C > G, c.1139 + 1G > A), one nonsense mutation (p.Gln414*) and one frameshift mutation (p.Pro420Leufs*440). Eighteen mutations have been reported earlier. Among these p.Ser287Leu (8.82%), p.Phe216Ser (7.35%), p.Asn32Thr (6.61%) and p.Ala291Ser (5.88%) were the most frequent mutations in Indian patients but were rare in the mutational profiles reported in other populations. These results indicate that the Indian patients may have a distinct mutation spectrum compared to those of other populations. Mutant alleles in exon 1, 7 and 8 accounted for 44.8% of the mutations, and sequencing of these exons initially may be a cost-effective approach in Asian Indian patients. This is the largest study on molecular analysis of patients with MPS IVA reported in the literature, and the first report from India
    American Journal of Medical Genetics Part A 09/2014; · 2.30 Impact Factor
  • Neerja Gupta, Madhulika Kabra, Seema Kapoor
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    ABSTRACT: 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.
    Indian pediatrics 09/2014; 51(9):693-6. · 1.01 Impact Factor
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    ABSTRACT: AbstractBackground
    Vaccine 08/2014; 32, Supplement 1:A104-A109. · 3.49 Impact Factor
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    ABSTRACT: This study was undertaken in view of the paucity of data regarding the profile of prothrombotic factors in children with ischemic stroke. Sixty-four children with ischemic stroke were prospectively evaluated for presence of prothrombotic factors over a 2 year period. The blood samples were analyzed for protein C (PC), protein S (PS), activated protein C resistance (APCR), factor V Leiden (FVL), anti-thrombin-III (AT-III), lipoprotein (a) [Lp(a)], lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL) immunoglobulin (Ig) M and IgG, homocysteine, and methylenetetrahydrofolate reductase (MTHFR) at least 3 months after the onset of stroke. At least one prothrombotic factor was identified in 45.3% children (29/64). These included hyperhomocysteinemia (11/64), PC deficiency (9/64), aCL (8/64), PS deficiency (5/64), APCR (3/64), AT-III deficiency (2/64) and LA (1/64). Multiple factors were coexistent in 17.2% (11/64). The prevalence of PC deficiency, PS deficiency and co-existence of multiple abnormalities observed were similar to the published literature. Elevated Lp(a) and APCR were less prevalent. FVL and MTHFR were not seen in any of the study children. Forty-five percent of children had at least one prothrombotic abnormality. Hyperhomocysteinemia, PC deficiency, aCL and PS deficiency were the most frequent prothrombotic abnormalities.
    Journal of Clinical Neuroscience 08/2014; · 1.32 Impact Factor
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    ABSTRACT: This cross sectional study assessed the prevalence of behavioral comorbidity and its association with epilepsy-related factors in children and adolescents with epilepsy. One hundred consecutive patients with active epilepsy, aged 6–16 years, were screened for behavioral comorbidity using the Child Behavior Checklist and those who qualified as having behavioral comorbidity were compared with those who did not have it. Behavioral comorbidity was found in 43 of 100 participants. Being treated with antiepileptic drug polytherapy (odds ratio 6.3, 95% confidence interval 1.4–17.3, p = 0.01) independently predicted behavioral comorbidity in the patients studied. The demonstrated high frequency of behavioral comorbidity in children with epilepsy suggests that pediatrician and pediatric neurologists should be sensitive to this fact in order to identify behavioral comorbidity in children with epilepsy.
    Journal of Clinical Neuroscience 08/2014; · 1.32 Impact Factor
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    ABSTRACT: Iodine deficiency (ID) is an endemic health problem in Kangra District, Himachal Pradesh (HP) state. ID leads to mental retardation, deaf mutism, squint, dwarfism, spastic diplegia, neurological defects and congenital anomalies. Iodine nutrition status amongst neonates can be assessed by estimating Thyroid Stimulating Hormone (TSH). The present study was conducted with an objective to assess the iodine nutrition status amongst Neonates in Kangra district, HP. All of the hospitals in the district which provide obstetric services were enlisted, of which three were selected for this survey. A total of 613 umbilical cord blood samples of neonates were collected on filter paper and analyzed for TSH. WHO (2007) reported that that a < 3% frequency of TSH concentrations above 5mIU/L in samples collected 3-4 days after birth indicates iodine sufficiency in a population. In our study we found that 73.4% of the neonates had TSH levels of more than 5mlU/l, thus indicating ID in the population studied. Iodine deficiency continues to be a public health problem in Kangra district, Himachal Pradesh.
    Journal of Trace Elements in Medicine and Biology 07/2014; · 2.49 Impact Factor
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    ABSTRACT: Background Sulfatides, the most abundant glycosphingolipids, are a major component of myelin. They are degraded by the combined action of sphingolipid activator protein and arylsulfatase A. Deficiency of either of these two causes metachromatic leukodystrophy (MLD). On the basis of age of onset this entity is divided into late infantile, juvenile and adult subtypes. Late infantile form, the commonest subtype, can have peripheral neuropathy as the initial manifestation. The other two usually manifests peripheral neuropathy later in the disease course. Case An 1.5 year old girl with preexisting isolated motor delay presented with acute onset ascending flaccid quadriparesis, ptosis and respiratory failure. Ptosis and respiratory failure responded completely to intravenous immunoglobulin whereas quadriparesis showed minimal improvement. Nerve biopsy revealed metachromatic granules with demyelination and serum arylsulfatase A levels were undetectable. Conclusion The severity and nature of the disease coupled with the response to immunotherapy makes this case unusual. This case represents either an atypical presentation of MLD with coincidental response to immunotherapy or an episode of immune mediated neuropathy in a case of MLD as they already have diseased nerves.
    Pediatric Neurology 06/2014; · 1.50 Impact Factor
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    ABSTRACT: Background Congenital Ichthyosis especially in darker skin types is at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis.Objective To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital IchthyosisMethods In this cross sectional study,119 children with Ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase(ALP) were measured. Radiological screening for rickets was carried out only in Ichythoses children.Results47 (41%) children with ichthyosis had either clinical or radiological evidence of rickets. Correlation between serum 25(OH)D and PTH showed a serum level of 25(OH)D 8ng/mL, was associated with significant increase in PTH. Correlation between PTH and ALP showed that a serum PTH level of 75 pg/mL was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores as compared to common ichthyosis.Conclusions Serum levels of 25(OH)D ≤ 8 ng/mL and PTH (≥ 75 pg/mL) significantly increases the risk for development of rickets (OR = 2.8; 95% CI = 1.05 – 7.40;P = 0.04) in ichthyosis. Among the different types, ARCI (OR 4.83; 95% CI 1.74 – 13.45; p < 0.01) and EI (OR 5.71; 95% CI 1.74 – 18.79; p < 0.01) are at an increased risk of developing rickets.This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 05/2014; 172(1). · 3.76 Impact Factor
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    ABSTRACT: Background:Iodine deficiency disorder (IDD) is a public health problem in Uttarakhand state.Objective:The present study was conducted in district Udham Singh Nagar, Uttarakhand state with an objective to assess the status of iodine deficiency amongst school age children (6-12 years).Materials and Methods:Thirty clusters were selected by utilizing the population proportionate to size (PPS) cluster sampling methodology. A total of 1807 children in the age group of 6-12 years were included. The clinical examination of the thyroid of each child was conducted. Urine and Salt samples were collected from children.Results:The Total Goiter Rate (TGR) was found to be 13.2%. The proportion of children with Urinary Iodine Excretion (UIE) level <20, 20-49, 50-99, 100-199 and ≥200 μg/l was found to be nil, 6.0, 21.2, 34.2 and 38.5 percent, respectively. The median UIE level was 150 μg/l. Only 46.7% of the salt samples had stipulated level of iodine of 15 ppm and more.Conclusion:The study population had mild degree of public health problem of iodine deficiency.
    Indian journal of endocrinology and metabolism. 05/2014; 18(3):419-21.
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    ABSTRACT: Iodine deficiency (ID) is an endemic health problem in Kangra District, Himachal Pradesh (HP). ID in pregnant mothers leads to neonatal hypothyroidism (NH), mental retardation, deaf mutism, squint, dwarfism, spastic dysplasia, neurological defects and congenital anomalies. NH can be assessed by estimating the thyroid stimulating hormone (TSH) in cord blood samples. The present study was conducted with an objective to assess the prevalence of NH in district Kangra, HP. In district Kangra, all the hospitals providing obstetric services were enlisted. Three hospitals conducting more than 100 deliveries per year were selected randomly. A total of 613 umbilical cord blood samples of neonates were collected on filter papers and analyzed for TSH. TSH was estimated by enzyme-linked immunosorbent assay method. Neonates with TSH levels ⩾20 mIU/l were recalled for reassessment of TSH for confirmation of NH. Prevalence of NH was found to be 4.4%. This finding suggests the need for the implementation of a neonatal screening program for early detection of children with ID.European Journal of Clinical Nutrition advance online publication, 23 April 2014; doi:10.1038/ejcn.2014.71.
    European journal of clinical nutrition 04/2014; · 3.07 Impact Factor
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    ABSTRACT: Osteogenesis imperfecta (OI) is a condition of decreased bone density with heterogeneous etiologies. Most of the cases are inherited in an autosomal dominant fashion and are caused by mutations in the COL1A1 or COL1A2 genes. Since these two genes are very large, there are no data about mutations in Indian patients with OI. We selected 35 Indian patients who were clinically diagnosed with OI and all exons of both the genes were sequenced. Mutations in COL1A1 (14 cases, 6 novel) and COL1A2 (11 cases, 7 novel) were identified in 25 patients. A total of 55 polymorphisms were identified in both the genes with eight novel variants in the coding region, and nine novel variants in the non-coding regions. No mutation was detected in 10 patients. Six of them were from consanguineous families, with one or two similarly affected siblings suggesting possible autosomal recessive inheritance. If we exclude families with consanguinity, mutations were identified in 25 out of 29 families giving 86% mutation detection rate. Mutations in COL1A1 accounted for 56% of the cases and COL1A2 44%, which is similar to the reported rate worldwide. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 03/2014; · 2.30 Impact Factor
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    ABSTRACT: Holoprosencephaly (HPE) is the most common forebrain developmental anomaly with a prevalence of 1:16 000 live-births. Possible aetiological agents include environmental factors and genetic defects such as trisomies (13, 18) and deletions (18p, 7q, 2p and 21q). This complex malformation is due to incomplete division of the cerebral hemisphere. The phenotypes of HPE include alobar, semilobar, lobar and midline interhemispheric fusion variants. Craniofacial anomalies occur in 80% of cases. Severely affected babies die in the neonatal period. Here we report an autopsied case of semilobar HPE with pituitary and adrenal agenesis with 21q22 deletion. Additional findings are noted that would help expand the spectrum of 21q22 deletion.
    Case Reports 03/2014; 2014.
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    ABSTRACT: Fungal infections, especially in immunocompetent children are uncommon causes of fever of unknown origin. A 5-year-old boy with prolonged fever and no evidence of immunosuppression. Ultrasound-guided retroperitoneal lymph node biopsy showed granulomas and intracytoplamic fungal yeasts; staining charactristics were suggestive of cryptococci. Clinical and radiological improvement was seen after treatment with amphoterecin-B. Disseminated fungal infection should be suspected as a cause of pyrexia of unknown origin after ruling out the commoner causes. Biopsy from enlarged lymph node or organomegaly may yield the diagnosis when non-invasive tests fail.
    Indian pediatrics 03/2014; 51(3):225-6. · 1.01 Impact Factor
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    ABSTRACT: Context:Menkes disease is an X-linked multisystem disorder characterized by early onset of cerebral and cerebellar neurodegeneration, fair skin, hypopigmented sparse hair and connective tissue abnormalities.Aims:We aimed to evaluate the clinical, electrophysiological and radiological features of children with Menkes disease seen at our institute.Setting/Design:The medical records of children diagnosed with Menkes disease admitted in the pediatric neurology ward or attending the special pediatric neurology clinic at a tertiary care and a referral hospital in North India, from January 2010 to December 2012, were retrospectively reviewed. The clinical data of each case was subsequently summarized and reported.Statistical analysis used:Descriptive statistics were used.Results:During the study period, 1174 children were seen. Out of these, 6 cases were diagnosed as Menkes disease on the basis of clinical phenotype, low serum copper and ceruloplasmin and supportive neuroimaging. All the children were males and had disease onset within 3 months of age, with 4 children presenting in the neonatal period. Global developmental delay and refractory seizures were the predominant clinical symptoms. Two children had symptomatic West syndrome. Other seizure semiologies included tonic-clonic (4), myoclonic (2) and tonic seizures (1). The electroencephalographic abnormalities included hypsarrythmia (2) and multifocal epileptiform discharges (3). The salient radiological features included white matter changes, temporal lobe abnormalities, global atrophy, subdural hygromas and tortuous cerebral blood vessels.Conclusions:Menkes disease should be suspected in a case of refractory early onset seizures especially in the presence of subtle clinical clues. The neuroimaging findings may further support the diagnosis.
    Journal of Pediatric Neurosciences 03/2014; 9(1):11-6.
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    ABSTRACT: To study the feasibility and value of postmortem fetal infantogram (X-ray film) in pregnancies terminated for prenatally diagnosed fetal congenital malformations and stillborn fetuses with congenital anomalies. Forty-two fetuses were diagnosed antenatally by ultrasonography to have fetal congenital malformation, 36 couples opted for medical termination of pregnancy (MTP) and intrauterine death (IUD) occurred in six cases. Informed written consent for autopsy including infantogram was given by 41 couples, one couple permitted only radiographs. On infantogram, the antenatal ultrasound diagnoses were confirmed in all the cases of central nervous system anomalies, but were not useful for genitourinary anomalies or cardiac anomalies. In five cases of antenatally suspected skeletal anomalies, radiographs changed the diagnosis of thanatophoric dwarf to osteogenesis imperfecta type llC in one case and achondrogenesis type 1B in another case. Infantogram made the syndromic diagnosis in three cases—sirenomelia, Roberts syndrome and caudal regression syndrome. Congenital diaphragmatic hernia was diagnosed at infantogram in a case missed on ultrasound. In three cases of nonimmune hydrops, X-ray films correlated with ultrasound findings, but could not find the cause. If autopsy, the ‘goal standard’ test is refused or cannot be done, at least an infantogram should routinely be done in pregnancies terminated for prenatally diagnosed fetal congenital malformations and stillborn fetuses with congenital anomalies, as it is noninvasive, easily available and consent given. It may change the diagnosis and counseling for future pregnancies, hence very useful in perinatal medicine.
    Journal of Fetal Medicine. 03/2014; 1(1):33-39.

Publication Stats

1k Citations
519.69 Total Impact Points


  • 1994–2014
    • All India Institute of Medical Sciences
      • Department of Paediatrics
      New Dilli, NCT, India
  • 2013
    • Dayanand Medical College & Hospital
      • Department of Pediatrics
      Ludhiana, Punjab, India
    • Tulane University
      • Hayward Genetics Center
      New Orleans, Louisiana, United States
  • 2012–2013
    • Charité Universitätsmedizin Berlin
      • Institute of Medical Genetics and Human Genetics
      Berlin, Land Berlin, Germany
  • 2008–2013
    • AIIMS Bhopal All India Institute of Medical Sciences
      Bhopal, Madhya Pradesh, India
  • 2007
    • Dr. Harisingh Gour University
      • Department of Pharmaceutical Sciences
      Sāgar, State of Madhya Pradesh, India