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Objective Fourth ventricular and juxta fourth ventricular arachnoid cysts (ACs) are rare clinical entities. Conventionally, ACs are managed with either micro-surgical excision or cerebrospinal fluid (CSF) diversionary procedures such as a shunt. Effective treatment modality still remains controversial. Advances in neuroendoscopy have helped in the effective management of this benign condition in a minimally invasive method. Description of a subset of patients with fourth ventricular and juxta fourth ventricular ACs and hydrocephalus who underwent transaqueductal cysto-ventriculostomy with a flexible neuroendoscope was the objective of this study. Methods This study included the data of patients with fourth ventricular and juxta fourth ventricular ACs and hydrocephalus operated between 2008 and 2019. Of 350 intraventricular neuroendoscopic procedures done during the last 11 years, 8 had obstructive hydrocephalus due to fourth ventricular and juxta ventricular arachnoid cyst. Endoscopic transaqueductal cystoventriculostomy and transaqueductal shunt placement was done in all using a flexible neuro-endoscope. Results Patients were aged 20 days to 15 months; in the neonate, the diagnosis was established during routine antenatal screening. Surgical procedure was done using a flexible neuro-endoscope. All improved symptomatically, radiologically and are on regular follow-up to date. One patient had postoperative meningitis, which gradually improved with antimicrobial therapy. None required alternative form of treatment such as shunt or craniotomy and microsurgical excision. Conclusion Endoscopic transaqueductal cysto-ventriculostomy is a safe, effective and minimal invasive modality in the hands of an experienced neurosurgeon for the management of fourth ventricular and juxta ventricular arachnoid cysts.

To assess the Common Sense Model among parents of children with neurological disorders, by determining the prevalence of symptoms of anxiety and depression, and how illness perceptions relate to symptoms of anxiety and depression both directly, and indirectly via coping.205 parents of children with neurological disorders in Hyderabad, India completed questionnaires.Hospital Anxiety and Depression Scale, Brief Illness Perception Questionnaire and Coping Health Inventory for Parents. We used multiple regressions and PROCESS for SPSS to assess direct and indirect relationships.Mild to severe symptoms of anxiety (41.0%) and depression (39.5%) were common. Symptoms of anxiety and/or depression were related to perceived treatment control over the illness, perceived understanding of the illness, perceived personal control over the illness (anxiety only), and perceived timeline of the illness (depression only). The coping strategy 'maintaining social support' mediated the relationship between symptoms of depression and four illness perceptions: perceived consequences (95%CI=.03,-.21), timeline (95%CI=.01,-.25), perceived personal control (95%CI=.02-.24), and treatment control (95%CI=.01-.34).Our findings have implications for education interventions to improve community attitudes of child neurological disorders. Such interventions may allow families' social networks to provide more support to parents, which could aid parents' coping strategies.

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%).

Many common household herbal preparations may have seizurogenic ingredients. We report 15 children with seizures following exposure to such compounds: oral ingestion of liquid preparation in 13, and local application of balm and Eucalyptus oil ingestion in one each. All children, except one, had generalized seizures. This study highlights the need to address this history during evaluation of first seizure, and increase awareness of seizurogenic potential of such preparations.

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.

Aicardi-Goutières syndrome (AGS) induces innate immune activation. It can present with cerebral calcifications and hepatosplenomegaly mimicking congenital infections. The present case report discusses the diagnosis and treatment of a case of fetal cardiomyopathy whose postnatal symptoms resembled TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, herpes and syphilis) infection. The mother had a history of two lost pregnancies due to fetal cardiomyopathy and the same was identified in the current pregnancy. At 34 weeks of gestation, the mother delivered a late preterm male neonate due to intrauterine growth restriction weighing 1590 g with respiratory distress and cardiomyopathy at birth. The neonate had cerebral calcifications, hepatosplenomegaly and thrombocytopenia. As the infant’s TORCH IgM titre was negative, pseudo-TORCH syndrome similar to AGS was suspected. Clinical exome sequencing of the parents and fetus identified no genes for hydrops fetalis or fetal cardiomyopathy; however, the AGSTREX1gene was identified in the neonate, while additional symptoms resembled TORCH infection. The neonate was discharged and has shown improvement with oral baricitinib treatment for the last 9 months.

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.

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.

To prospectively study the effectiveness and safety of clobazam as an add-on therapy in patients with epilepsy whose seizures are not adequately controlled with antiseizure medicine (ASM) monotherapy.We conducted a prospective, observational study at 28 neurology outpatient clinics in India from June 2017 to October 2019. Consecutive patients with epilepsy (older than 3 years) with inadequate seizure control with ASM monotherapy were initiated on clobazam. Patients were followed up at 1, 3, 6, 9, and 12 months. Seizure control and adverse events were assessed through personal interviews and seizure diaries.Out of 475 eligible patients, data of 429 patients (men: 65.5%) were evaluated (46 excluded due to protocol deviations). The median age was 25 (range, 3-80 years) years and the median duration of epilepsy was 3 (0.1-30) years. The majority of patients had focal epilepsy (55.0%) and genetic generalized epilepsy (40.1%). The one-year follow-up was completed by 380 (88.5%) patients. At one-year follow-up, 317 (83.4%; N = 380) patients in the study remained seizure free. These 317 patients who were seizure free at 12 months comprised 73.9% of the evaluable population (N = 429). In 98.8% of patients, the primary reason for adding clobazam was inadequate control of seizures with treatment. During one-year follow-up, a total of 113 (22.6%) patients experienced at least one adverse event which included 103 (20.6%) patients who experienced 386 episodes of seizures.The study provides preliminary evidence that clobazam is effective and well-tolerated as add-on therapy for a period of one year among patients with epilepsy inadequately stabilized with monotherapy.CTRI/2017/12/010906.

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.

In this study we present the first two cases from India of a rare inborn error of metabolism manifesting as dystonia and 3-methylglutaconic aciduria and a Leigh like lesions in the brain MRI associated with SERAC1 gene mutation, a phenotype characteristic of MEGDEL syndrome. A four base pair duplication in exon 15 i.e.NM_032861.3 (SERAC1) c. 1643_1646 dup ATCT (p.(Leu550SerfsX19)) and another with a homozygous missense variation in exon 15 i.e. NM_032861.3 (SERAC1) c.1709 G > A (p.(Gly526Glu)) were detected and both were novel mutations. Hepatopathy was observed in the neonatal period with lactic acidosis in one child and at the age of 5yrs in the other. These cases add to the existing number of patients identified till today and additional mutations in the SERAC1 gene.

Background Several genes have been implicated in a highly variable presentation of developmental delay with psychomotor retardation. Mutations in EMC1 gene have recently been reported. Herein, we describe a proband born of a consanguineous marriage, who presented with early infantile onset epilepsy, scaphocephaly, developmental delay, central hypotonia, muscle wasting, and severe cerebellar and brainstem atrophy. Methods Genetic testing in the proband was performed using custom clinical exome and targeted next‐generation sequencing. This was followed by segregation analysis of the variant in the parents by Sanger sequencing and evaluation of the splice variant by RNA sequencing. Results Clinical exome sequencing identified a novel homozygous intronic splice variant in the EMC1 gene (chr1:19564510C>T, c.1212 + 1G>A, NM_015047.2). Neither population databases (ExAC and 1000 genomes) nor our internal database (n = 1,500) had reported this rare variant, predicted to affect the splicing. RNA sequencing data from the proband confirmed aberrant splicing with intron 11 retention, thereby introducing a stop codon in the resultant mRNA. This nonsense mutation is predicted to result in the premature termination of protein synthesis leading to loss of function of the EMC1 protein. Conclusion We report, for the first time the role of aberrant EMC1 RNA splicing as a potential cause of disease pathogenesis. The severe epilepsy observed in our study expands the disease‐associated phenotype and also emphasizes the need for comprehensive screening of intronic splice mutations.

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.

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: Glutaric aciduria type I is an autosomal recessive organic acid disorder. The primary defect is the deficiency of Glutaryl-CoA dehydrogenase (EC number 1.3.99.7) enzyme that is involved in the catabolic pathways of the amino acids L-lysine, L-hydroxylysine, and L-tryptophan. It is a treatable neuro-metabolic disorder. Early diagnosis and treatment helps in preventing brain damage. Methods: The Glutaryl-CoA dehydrogenase gene (GCDH) gene was sequenced to identify disease causing mutations by direct sequencing of all the exons in twelve patients who were biochemically confirmed with GA I. Results: We identified eleven mutations of which nine are homozygous mutations, one heterozygous and two synonymous mutations. Among the eleven mutations, four mutations p.Q162R, p.P286S, p.W225X in two families and p.V410M are novel. A milder clinical presentation is observed in those families who are either heterozygous or with a benign synonymous SNP. Multiple sequence alignment (MSA) of GCDH with its homologues revealed that the observed novel mutations are not tolerated by protein structure and function. Conclusions: The present study indicates genetic heterogeneity in GCDH gene mutations among South Indian population. Genetic analysis is useful in prenatal diagnosis and prevention. Mutation analysis is a useful tool in the absence of non-availability of enzyme assay in GA I.

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.

In this study, we report three cases of nonketotic hyperglycinemia (NKHG) diagnosed biochemically and molecularly. Clinical exome analysis in two families revealed two novel mutations in the aminomethyltransferase (AMT) gene, that is, c.14_15insT (p.Ser6LysfsTer22) and c.259–2A > T, both of them adversely affecting the protein. This is the first report of AMT gene mutations in NKHG from India. Prenatal diagnosis in the first family showed an unaffected fetus in the third pregnancy. The role of AMT protein is pivotal for the synthesis of 5,10-methylene tetrahydrofolate, the first metabolite in one-carbon metabolism that regulates DNA synthesis, repair, and methylation.

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.