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Background: GeneXpert MTB/RIF is a test for early, rapid diagnosis of tubercular meningitis (TBM). Aim: The aim of this article was to study the clinical profile, radiological features, yield of GeneXpert, neurosurgical interventions, and outcome of TBM in children. Settings and Design: This was a retrospective and prospective observational study. Materials and Methods: Diagnosis was based on the uniform research definition criteria and was staged according to the British Medical Research Council. Mantoux test, analysis of cerebrospinal fluid (CSF), CSF GeneXpert, and radiological investigations were performed. Results: Of 36 patients, 50% were aged 1–5 years. Fever (100%), headache (82%), altered sensorium (80%), and vomiting (66%) were common features. Twelve (33%) had contact with active case of tuberculosis; 32 received Bacille Calmette Guarin vaccination. Neurological features included severe deterioration in sensorium (Glasgow Coma Scale < 8) (38%), mild and moderate deficit in sensorium (31%), hemiparesis (41%), and involvement of sixth (25%) and seventh (22%) cranial nerves. Cerebral vision impairment (25%), papilledema (25%), and dystonia (22%) were other findings. CSF GeneXpert was positive in 37% (12/33) patients. Hydrocephalus and basal exudates (75%) were noted on neuro-imaging. Surgical intervention was performed in children with hydrocephalus (13/27). Omayya reservoir was placed in seven children, of which five needed conversion to ventriculoperitoneal (VP) shunt; direct VP shunt was carried out in six (6/13). Good outcome was noted in 78% at discharge. Stage III TBM (P = 0.0001), cerebral infarcts (P = 0.0006), and motor deficits (P = 0.03) were associated with poor outcome. Sequelae included learning difficulties with poor scholastic performance (31.5%). Conclusion: GeneXpert has high diagnostic specificity, but negative results do not rule out TBM. CSF GeneXpert provided quick results. Placement of Ommaya reservoir in TBM stage II and III with hydrocephalus was not successful. Hydrocephalus was managed conservatively with success (53%).

High prevalence of congenital hypothyroidism (CH) among Indian newborns prompted us to establish population-specific reference ranges of TSH and to explore the contribution of the common genetic variants in TSHR, TPO, TG and DUOX2 genes towards CH. A total of 1144 newborns (593 males and 551 females) were screened for CH. SNV profiling (n = 22) spanning three candidate genes, i.e. TSHR, TPO and TG was carried out in confirmed CH cases (n = 45). In screen negative cases (n = 700), ten TSHR variants were explored to establish association with CH. No mutation found in DUOX2. The 2.5th to 97.5th percentiles of TSH in these newborns were 0.5 to 12.2 mU/L. In newborns with optimal birth weight, the cut-off was 10 mU/L. Lower or higher birth weight resulted in slightly higher TSH. Two TSHR variants, i.e. rs7144481 and rs17630128 were associated with agenesis, hypoplasia and goiter. The rs2268477 was associated with agenesis and hypoplasia. The rs1991517, rs2075176 and rs2241119 were associated with agenesis only. The rs7144481, rs17630128, rs1991517 and rs2268477 were associated with 2.17, 4.62, 2.91 and 2.29-fold increased risk for CH, respectively. Among the TPO variants, rs867983 and rs2175977 were associated with agenesis and goiter, respectively. Among the TG variants, rs2076740 showed association with agenesis and goiter. Two rare variants i.e. TPO g.IVS14-19 G>C and TG c.1262 C>T were observed in CH cases. No genetic variant identified in the two exons of DUOX2. To conclude, the current study established Indian population-specific normative values for TSH and demonstrates specific genotype–phenotype correlations among three candidate genes.

Background Joubert syndrome and related disorders are a group of ciliopathies characterized by mid-hindbrain malformation, developmental delay, hypotonia, oculomotor apraxia, and breathing abnormalities. Molar tooth sign in brain imaging is the hallmark for diagnosis. Joubert syndrome is a clinically and genetically heterogeneous disorder involving mutations in 35 ciliopathy-related genes. We present a large cohort of 59 patients with Joubert syndrome from 55 families. Molecular analysis was performed in 35 families (trio). Methods Clinical exome analysis was performed to identify causal mutations, and genotype-phenotype correlations were evaluated. Results All of the cases were stratified into pure Joubert syndrome (62.7%), Joubert syndrome with retinal disease (22.0%), polydactyly (8.5%), and liver (1.7%) and kidney (1.7%) involvement. Joubert syndrome-related disorders include Meckel-Gruber syndrome in 5.1% cases and Leber congenital amaurosis (1.7%). Of the 35 Joubert syndrome-related genes, 11 were identified in these patients, i.e., CEP290, C5ORF, TCTN1, CC2D2A, RPGRP1L, TCTN3, AHI1, INPP5E, TCTN2, NPHP1, and TMEM237. For the first time, we identified a ciliopathy gene, CCDC28B, as a causal gene in Joubert syndrome in one family. CEP290 accounted for 37.8% cases of pure Joubert syndrome, Joubert syndrome with retinal and renal disease, and Meckel-Gruber syndrome. The p.G1890∗ allele in CEP290 is highly recurrent. Of the six families with Joubert syndrome who had a prenatal diagnosis, one fetus was normal, two were carriers, and three were affected. Conclusions This is the largest study of Joubert syndrome from India. Although a high degree of locus and allelic heterogeneity was observed, CEP290 variants were the most common among these patients.

Objective Through international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1-related epilepsy and explored genotype-phenotype correlations associated with frequently encountered variants. Methods A cross-sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics. Results Twenty-seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two-thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray-white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%-50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy. Significance Our cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence-based practice is still unavailable.

When a child is diagnosed with epilepsy, counseling regarding the same is done by the treating doctor. Most parents are frightened and have poor knowledge about epilepsy. Therapeutic advice including drug dosage, administration and side effects takes up the major part of physician's time, thereby neglecting important issues like home seizure management, follow up and others. These lacunae in knowledge require systematic patient and family education. To address these issues, an expert group meeting of pediatric neurologists and epileptologists in India along with social workers/epilepsy educators, legal experts, parents, and teachers was held. The various aspects regarding parental counseling in children with epilepsy were discussed and a consensus document was formulated. Here authors present the group consensus statement on counseling parents and caregivers of children with epilepsy. This document is intended to help physicians and pediatricians counsel the families when a child is diagnosed with epilepsy.

We present the case of a 5-year-old girl who had six episodes of meningitis. She also had panhypopituitarism and was found to have a persistent craniopharyngeal canal (CPC) as the cause of her recurrent meningitis. Role of neuroradiology and a high index of suspicion by the clinical team are highlighted here. Persistent CPC is a rare cause of recurrent meningitis. We discuss the approach to the child with recurrent meningitis.

Summary Background The CNS manifestations of COVID-19 in children have primarily been described in case reports, which limit the ability to appreciate the full spectrum of the disease in paediatric patients. We aimed to identify enough cases that could be evaluated in aggregate to better understand the neuroimaging manifestations of COVID-19 in the paediatric population. Methods An international call for cases of children with encephalopathy related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and abnormal neuroimaging findings was made. Clinical history and associated plasma and cerebrospinal fluid data were requested. These data were reviewed by a central neuroradiology panel, a child neurologist, and a paediatric infectious diseases expert. The children were categorised on the basis of their time of probable exposure to SARS-CoV-2. In addition, cases were excluded when a direct link to SARS-CoV-2 infection could not be established or an established alternate diagnostic cause could be hypothesised. The accepted referral centre imaging data, from ten countries, were remotely reviewed by a central panel of five paediatric neuroradiologists and a consensus opinion obtained on the imaging findings. Findings 38 children with neurological disease related to SARS-CoV-2 infection were identified from France (n=13), the UK (n=8), the USA (n=5), Brazil (n=4), Argentina (n=4), India (n=2), Peru (n=1), and Saudi Arabia (n=1). Recurring patterns of disease were identified, with neuroimaging abnormalities ranging from mild to severe. The most common imaging patterns were postinfectious immune-mediated acute disseminated encephalomyelitis-like changes of the brain (16 patients), myelitis (eight patients), and neural enhancement (13 patients). Cranial nerve enhancement could occur in the absence of corresponding neurological symptoms. Splenial lesions (seven patients) and myositis (four patients) were predominantly observed in children with multisystem inflammatory syndrome. Cerebrovascular complications in children were less common than in adults. Significant pre-existing conditions were absent and most children had favourable outcomes. However, fatal atypical CNS co-infections developed in four previously healthy children infected with SARS-CoV-2. Interpretation Acute-phase and delayed-phase SARS-CoV-2-related CNS abnormalities are seen in children. Recurring patterns of disease and atypical neuroimaging manifestations can be found and should be recognised being as potentially due to SARS-CoV-2 infection as an underlying aetiological factor. Studies of paediatric specific cohorts are needed to better understand the effects of SARS-CoV-2 infection on the CNS at presentation and on long-term follow-up in children. Funding American Society of Pediatric Neuroradiology, University of Manchester (Manchester, UK). Video Abstract Neuroimaging manifestations in children with SARS-CoV-2 infection

Introduction The clinico-etiological spectrum of Acute leukoencephalopathy with restricted diffusion (ALERD) is not well known in Indian population. This is likely to vary between populations and ethnicities. Methods We retrospectively reviewed the clinicoetiological spectrum of ALERD at a tertiary care pediatric center, and described the clinical, imaging, etiological spectrum and short-term outcomes. Results Eleven out of 78 children with non-traumatic encephalopathy presenting to our center had a final diagnosis of ALERD. The mean age at presentation was 34.9 months (6–80 months) and 63.6% were males. The monophasic course (72.7%) and the diffuse pattern (63.6%) on neuroimaging were predominant in these children. Dengue haemorrhagic fever was the commonest underlying/triggering infection (5 of 11 children). Ten children required mechanical ventilation in view of neurogenic respiratory failure, with mean duration of ventilation of 6.4 days (Range 2–10 days). The duration of hospital stay varied from 11 to 25 days (Mean – 15.3 days). One child (9 %) died, 6 children (54.5 %) had varying degrees of cognitive impairment and 4 (36.3 %) children had a normal outcome. Children with a shorter duration of ventilation seemed to have a better outcome. Conclusion Dengue haemorrhagic fever was the commonest cause, and diffuse imaging pattern with monophasic course was the commonest presentation in Indian children with ALERD. The clinical presentation and factors influencing outcome are possibly different from previously described literature.

Hyperphosphatemia in the absence of renal failure is an unusual occurrence, particularly in children, but is a common primary feature of familial hyperphosphatemic tumor calcinosis. We report a child with hyperphosphatemia who presented with multiple episodes of neurologic dysfunction involving lower motor neuron facial nerve palsy along with sequential visual loss. He also had an episode of stroke. There was an extensive metastatic calcification of soft tissue and vasculature. Hyperphosphatemia with normal serum alkaline phosphatase, calcium, parathyroid hormone, and renal function was noted. He was managed with hemodialysis and sevelamer (3 months) without much success in reducing serum phosphate level, requiring continuous ambulatory peritoneal dialysis (3 years). Intact fibroblast growth factor 23 (FGF23) was undetectable, with C-terminal FGF23 fragments significantly elevated (2575 RU/ml, normal A (p.N162K) mutation in FGF23 exon 3, confirming the diagnoses of primary FGF23 deficiency, the first case to be reported from India.

Purpose The current study evaluates the etiology, clinical course and outcome of refractory convulsive status epilepticus (CSE) in older children. Methods Retrospective analysis of data of 73 children with CSE, aged ≥2 and ≤12 years was performed. Odds ratios were calculated between variables for clinical course and outcome. Mortality of the group was analyzed using survival analysis. Results Thirty three (45.2%) children progressed to refractory status epilepticus (RSE). The most common etiology for CSE was acute symptomatic in 44 (60.3%) of which 37 had presumed CNS infections. The odds of progressing to RSE were higher in children with acute symptomatic etiology (OR 2.62; CI – 95%; 0.99–7.14; p =0.041). Progression to RSE increased the chances of severe sepsis by six times (OR 6.08; CI – 95%; 1.19–31.02; p =0.036) and acidosis by nearly 15 times (OR 14.77; CI – 95%; 1.19–31.02; p =0.020). Overall mortality was 13.7%, higher in RSE (21.2% vs.7.5%). Amongst the 63 surviving children followed for 1 year from discharge, progression to RSE increased the odds of disability by seven times (OR 7.08; CI 29.31; p =0.004). Conclusion Acute symptomatic etiology was the commonest cause of CSE among older children from developing country and increased the odds of progressing to RSE. RSE was significantly associated with disability at 1 year from discharge.

Background: Juvenile idiopathic inflammatory myopathies (JIIM) are rare and heterogeneous. Subtype identification is important for treatment. Materials and Methods: Patients below 18 years diagnosed as idiopathic inflammatory myopathy (IIM) according to the Bohan and Peter criteria between January 2010 and May 2015 were evaluated with muscle biopsy in the four domains: muscle fiber, inflammation, connective tissue, and vascular, with basic panel of histochemical stains as per recommendations of the European Neuromuscular center (ENMC) workshop 2015. Immunohistochemistry with CD 31 was done to assess capillary density. Results: JIIM constituted 15.25% of IIM with juvenile dermatomyositis (JDM) being the most common subgroup (24/27) followed by juvenile overlap myositis (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). Muscle biopsy in JDM was characterized by perifascicular atrophy, necrosis, degeneration, and regeneration in all and the other features included perivascular inflammation (21), lymphoid aggregates (2), mitochondrial abnormalities (9), sarcoplasmic vacuoles (6), capillary dropout (5), capillary dilatation (6), and perimysial fibrosis (14). JOM was characterized by auto-antibodies and perivascular inflammation. Conclusion: JIIMs were rare and JDM was the most common subtype. Muscle biopsy evaluation as per ENMC criteria characterized the subgroups.

We describe an 11-month-old boy who presented with recurrent respiratory infections from 6 months of age. His elder sister died at 10 months with severe septicemia and meningitis. The boy had a mild motor delay. Investigations revealed T cell deficiency and very low serum uric acid suggestive of purine nucleoside phosphorylase (PNP) deficiency – a rare variant of severe combined immunodeficiency disease. A novel homozygous missense mutation of c.597C>G(p. S199R) of exon 5 on PNP gene confirmed the diagnosis. We suggest that uric acid should be a part of investigation profile for unidentified motor delay, as recurrent infections can be late presentation.

Rabies, a zoonotic viral encephalitis, continues to be a serious public health problem in India and several other countries in Asia and Africa. Survival is rarely reported in rabies, which is considered to be almost universally fatal. We report the clinical and radiological findings of eight patients with laboratory-confirmed rabies who survived the illness. With the exception of one patient who recovered with mild sequelae, all survivors had poor functional outcomes. The reported survival from rabies in recent years may reflect an increased awareness of the disease and greater access to better critical care facilities in rabies-endemic countries. Nonetheless, there is an urgent need to focus on preventive strategies to reduce the burden of this dreadful disease in rabies-endemic countries.

Background and Purpose: Muscle biopsy features of congenital muscular dystrophies (CMD) vary from usual dystrophic picture to normal or nonspecific myopathic picture or prominent fibrosis or striking inflammatory infiltrate, which may lead to diagnostic errors. A series of patients of CMD with significant inflammatory infiltrates on muscle biopsy were correlated with laminin α 2 deficiency on immunohistochemistry (IHC). Material and Methods: Cryostat sections of muscle biopsies from the patients diagnosed as CMD on clinical and muscle biopsy features from 1996 to 2014 were reviewed with hematoxylin and eosin(H&E), enzyme and immunohistochemistry (IHC) with laminin α 2. Muscle biopsies with inflammatory infiltrate were correlated with laminin α 2 deficiency. Results: There were 65 patients of CMD, with inflammation on muscle biopsy in 16. IHC with laminin α 2 was available in nine patients, of which six showed complete absence along sarcolemma (five presented with floppy infant syndrome and one with delayed motor milestones) and three showed discontinuous, and less intense staining. Conclusions: CMD show variable degrees of inflammation on muscle biopsy. A diagnosis of laminin α 2 deficient CMD should be considered in patients of muscular dystrophy with inflammation, in children with hypotonia/delayed motor milestones.

Spinal muscular atrophy with respiratory distress syndrome (SMARD1) is a rare cause of early infantile respiratory failure and death. No cases have been currently described from India. Two low-birth-weight infants presented prior to 6 months of age with recurrent apnea and respiratory distress. Both required prolonged ventilation, and had distal arthrogryposis and diaphragmatic eventration. Nerve conduction study revealed motor sensory axonopathy. Genetic testing confirmed mutations in immunoglobulin mu binding protein (IGHMBP2). These two cases establish presence of SMARD1 in our population. Both infants died on discontinuation of ventilation. Antenatal diagnoses done in one pregnancy. Though rare, high index of suspicion is essential in view of poor outcome and aid antenatal counseling.

Extra nodal presentation of Non Hodgkins Lymphoma (NHL) is a rare entity, and data available about the NHL that primarily involves of middle ear and mastoid is limited. We report a case of diffuse large B cell lymphoma (DLBCL), in a 2 year 8 month old boy, who developed otalgia and facial palsy. Computed tomography revealed a mass in the left mastoid. Mastoid exploration and histopathological examination revealed DLBCL. This case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and/facial palsy.

A 2-year 7-month-old girl born out of a consanguineous marriage, presented at our facility with clinical features characterized by the eyelid triad of blepharophimosis, blepharoptosis and epicanthus inversus in association with hypertelorism, cleft palate and craniosynostosis. This constellation of features is suggestive of Michels syndrome. At the time of writing this report, there were only ten reported cases worldwide and to the best of our knowledge, there have been no published reports from India.

Aims The objective of this study was to describe a cohort of infants with basal ganglia stroke associated with mineralization in the lenticulostriate arteries and their clinical outcomes. Method Subcortical strokes occurring in infants during the study period were categorized as arterial ischaemic, venous, or haemorrhagic. A cohort of infants with basal ganglia infarcts and associated mineralization of lenticulostriate arteries were identified. This group was analysed for possible aetiological factors, clinical course, and recurrence rate of the stroke. Results Of 23 infants with basal ganglia arterial ischaemic stroke, 22 (16 males, six females; mean age 11mo [±SD 4.8mo]) were found to have lenticulostriate artery mineralization. Twenty infants presented with hemiparesis and two presented with recurrent episodes of hemidystonia. Eighteen infants had a history of minor trauma before onset of stroke. No other predisposing factors were identified in this cohort. There were no demonstrable causes for vascular and soft tissue calcification. The mean follow-up was 11 months, during which five infants experienced stroke recurrence. Of the 17 infants who did not experience a recurrent stroke, eight exhibited complete neurological recovery, and nine had mild residual hemiparesis. Interpretation Acute basal ganglia stroke after minor trauma associated with mineralization of lenticulostriate arteries in infants is a distinct clinicoradiological entity. Investigations for prothrombotic states and vasculopathies are normal. Although neurological outcomes in most children are good, trauma is a risk factor for recurrence of stroke.

Background/Aims: Mutations in the inwardly-rectifying K+ channel KCNJ10/Kir4.1 cause an autosomal recessive disorder characterized by epilepsy, ataxia, sensorineural deafness and tubulopathy (EAST syndrome). KCNJ10 is expressed in the kidney distal convoluted tubule, cochlear stria vascularis and brain glial cells. Patients clinically diagnosed with EAST syndrome were genotyped to identify and study mutations in KCNJ10. Methods: Patient DNA was sequenced and new mutations identified. Mutant and wild-type KCNJ10 constructs were cloned and heterologously expressed in Xenopus oocytes. Whole-cell K+ currents were measured by two-electrode voltage clamping. Results: Three new mutations in KCNJ10 (p.R65C, p.F75L and p.V259fs259X) were identified, and mutation p.R297C, previously only seen in a compound heterozygous patient, was found in a homozygous state. Wild-type human KCNJ10-expressing oocytes showed strongly inwardly-rectified currents, which by comparison were significantly reduced in all the mutants (p < 0.001). Specific inhibition of KCNJ10 currents by Ba2+ demonstrated residual function in all mutant channels (p < 0.05) but V259X. Conclusion: This study confirms that EAST syndrome can be caused by many different mutations in KCNJ10 that significantly reduce K+ conductance. EAST syndrome should be considered in any patient with a renal Gitelman-like phenotype with additional neurological signs and symptoms like ataxia, epilepsy or sensorineural deafness.

We describe the clinical features, investigations and outcome of 4 adolescents aged 13, 16, 17 and 19 years, with fixed dystonia. The diagnosis was made within 6 months of the onset of symptoms. One patient had an identifiable traumatic precipitant. All the affected extremities had pain, sudomotor and vascular changes which were consistent with complex regional pain syndrome. The extremities affected by dystonia were the foot and the hand. The dystonia spread to affect other extremities in one patient. One patient had hemifacial spasm. Examination of the central and peripheral nervous system and allied investigations failed to reveal an organic cause. Common genetic causes for dystonia were excluded. The response to physical treatments for the affected extremities, such as Botulinum Toxin and surgery was poor. In all our cases there were significant psychological and psychiatric factors. Three patients fully met the criteria for psychogenic dystonia and responded well to psychological intervention. Fixed dystonia in adolescents is an uncommon disorder of unknown aetiology, usually presenting in girls, which can be very disabling and difficult to treat. The affected parts of the body are usually painful and show vascular changes. The condition is allied to CRPS. Treatment with multidisciplinary approach including psychological measures and physiotherapy is more likely to be successful and may prevent unnecessary physical measures.

A term baby developed hypoventilation on day 1 of life requiring mechanical ventilation and had subsequent difficulty in weaning. Diagnostic workup for pulmonary, cardiac, metabolic, sepsis and structural CNS diseases were negative. In view of persistent hypoventilation despite raised pCO(2) levels in absence of any sedation, the diagnosis of Idiopathic. Congenital Central Hypoventilation Syndrome (CCHS) was considered. The baby was tested for Paired-like Homeobox 2B (PHOX2B) gene mutation and was found to have expanded alleles containing 10 polyalanine repeats producing genotype of 20/30 on chromosome 4p12 (The normal being 20/20). This is the first report of a neonate from India with genetically confirmed CCHS.

To the Editor: Non-immune hydrops fetalis (NIHF) is caused by a variety of disorders recently classified in over 6000 individuals. The main causes are cardiovascular disorders (21 %), anemia (10 %), chromosomal and metabolic inborn errors of metabolism (IEM) disorders (20 %); however in 20–25 % of NIHF cases, the cause remains unexplained [1]. Among IEM cases, only 15 cases of congenital disorder of glycosylation (CDG) presenting with NIHF have been reported [2]. We report here a case of NIHF which was later found to be associated with CDG and its various progressive multisystem manifestations. A 34 wk preterm, antenatally diagnosed case of hydrops fetalis was delivered because of fetal distress. She was managed as per the protocol and investigated for possible causes of hydrops fetalis (HF). Immunemediated cause was ruled out with detailed investigations. Echocardiography was normal. USG abdomen showed moderate ascites which resolved within 2 wk. No obvious malformations or dysmorphism were noticed. Second week of life screening showed evidence of congenital hypothyroidism with normal total T4 (11.6 μg/dl), low free T4 (0.5 ng/L) and an elevated thyroid stimulating hormone (TSH 47.8mIU/L). TSH level was normalized over 4 wk with thyroxine treatment. As per few earlier reports, association of NIHF with congenital hypothyroidism was suspected and monitoring and follow up were planned [3]. During next 6 mo she developed recurrent pericardial effusion with no specific etiology. She also developed seizures and generalized hypotonia, failure to thrive, hepatosplenomegaly and coarse facial features. CT chest and abdomen showed pericardial effusion, hepatomegaly with fatty infiltration and bilateral enlarged kidneys. Metabolic workup and urinary glycosaminoglycans (GAG) were normal. Congenital disorders of glycosylation was suspected and isoelectric focusing (IEF) of serum transferrin was done that suggested diagnosis of CDG-Ia, but over next 3 d she died due to massive pericardial effusion and cardio respiratory arrest (Fig. 1). Genetic testing of the parents or child could not be done; however literature suggests CDG type-Ia (PMM2) as the most frequent form of CGD which is caused by deficiency of phosphor manno mutase (PMM) enzyme and associated with mutations in the PMM2 gene located on chromosome 16p13 [4].

A 27-year-old pregnant woman underwent ultrasonography at 36 weeks gestation, which revealed unilateral echogenic lesion (figure 1). Her previous week's scan was normal. Possibilities of intracerebral hemorrhage and neoplasm were considered. The neonate, delivered 7 days later, had seizures on day 1. The MRI revealed bilateral extensive supratentorial intracerebral hemorrhages (figure 2). The baby died 3 days later due to continuing seizures and raised intracranial pressure. The MRI was characteristic of deep medullary vein (DMV) thrombosis with secondary hemorrhagic infarction. Prothrombotic workup revealed antithrombin III deficiency. The radiating fan-shaped hemorrhages are unique imaging findings of DMV thrombosis, causing substantial morbidity.1,2

Case 1 is a 28 months female child, who has been symptomatic from 8 month of age with multiple, painful bruises over legs once in 5 to 6 weeks. Her complete blood picture was normal.PT and APTT were prolonged with normal fibrinogen and liver function. Case 2, became symptomatic from day 2 of life. He was treated for blood stained vomiting and black coloured stool and severe anaemia. Second episode was subdural hemorrhage and seizures. Investigations revealed abnormal PT and APTT with normal fibrinogen and liver function. Hereditary prothrombin deficiency is one of the rare congenital coagulation defect encountered in clinical practice. High index of suspicion is required to diagnose this condition with systematic approach as the facility to check factor 2 levels are not freely available in many centres. Bleeding manifestations are dependent on factor level. Children with severe deficiency are prone for life threatening bleeds. We report couple of children who had severe form of hereditary prothrombin deficiency with variable clinical manifestations. In both the cases, coagulation profile was suggestive of common pathway defect, PT and APTT were prolonged. Fibrinogen and Liver function tests were normal. No evidence of sepsis, no response to vitamin K. Further evaluation revealed low prothrombin activity (

Beta-ketothiolase deficiency, or mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is a rare autosomal recessive disorder affecting isoleucine catabolism and ketone body metabolism. A patient from South India presented with acute ketoacidosis at 11 months of age. During the acute crisis the C5OH (2-methyl-3-hydroxybutyryl) carnitine and C5:1 (tiglyl) carnitine were elevated and large amounts of 2-methyl-3-hydroxybutyrate, tiglylglycine, and 2-methylacetoacetate were excreted. Brain CT showed bilateral basal ganglia lesions. Potassium ion-activated acetoacetyl-CoA thiolase activity was deficient in the patient's fibroblasts. The patient is a homozygote for a novel c.578T>G (M193R) mutation. This is the first report of T2 deficiency confirmed by enzyme and molecular analysis from India.

An 8-year-old girl presented with a 5-day history of double vision on attempting to look downward. Examination of her eye movements revealed weakness of bilateral superior oblique muscles, with a normal examination otherwise. The brain MRI revealed a cysticercal granuloma of the midbrain ventral to the cerebral aqueduct with perilesional edema, sparing both red nuclei, and giving the appearance of “face of panda” (figure, A and B). The face of panda sign has been described in cases of Wilson disease, including “face of giant panda” and “face of panda cub” in the midbrain and pons, respectively.1,2

Gray hair syndromes are rare syndromes which have an autosomal recessive inheritance and are characterized by pigmentary dilution of skin and hair, defects in immunological function, and nervous system defects. They comprise three disorders namely Chediak–Higashi syndrome (CHS), Griscelli syndrome (GPS), and Elejalde syndrome. Clinically, it is difficult to distinguish these disorders as their clinical features may overlap. Hence, to make a correct diagnosis and differentiate between CHS and GPS light microscopic examination of skin and hair shafts as well as peripheral blood smear evaluations should be done. In cases where the diagnosis is not possible chromosomal analysis for specific mutations can be done. In resource-poor settings where chromosomal analysis is not possible, and light microscopy findings are inconclusive, polarized microscopy can serve as a useful tool to distinguish between CHS and GPS. We report three cases with gray hair syndromes where the diagnosis on light microscopy and polarized microscopy of hair shaft correlated with the bone marrow examination findings and chromosomal analysis, thus emphasizing the importance of a noninvasive, cost-effective, and time-saving alternative in the diagnosis of these syndromes.

OBJECTIVE: To study the effect of a single dose of sodium bicarbonate given during neonatal resuscitation at birth on the acid–base status on the first day of life. SETTING: Tertiary care Level III NICU. STUDY DESIGN: A total of 55 consecutively born asphyxiated neonates continuing to receive positive pressure ventilation at 5 minutes of life were randomized to receive either 4 ml/kg (1.8 meq/kg) of sodium bicarbonate or 5% dextrose. RESULTS: The mean pH, base deficit and PaCO2 were similar between the Base group and the Control group for the first 24 hours of life. The number of babies with persistent metabolic acidosis at 1, 6, 12 and 24 hours were comparable between the two groups. CONCLUSION: Sodium bicarbonate given during neonatal resuscitation did not change the acid–base status in the first 24 hours of life.

Herein, we describe our experience with six Pompe patients in South India from September 2007 to July 2012. All patients were diagnosed at our centre by clinical exam and confirmed with enzyme assays and DNA analyses.