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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.

Accidental ingestion of phenytoin can lead to severe neurological sequelae. Charcoal hemoperfusion decreases phenytoin levels but has never been reported before in children. We present a child with accidental ingestion of phenytoin who responded to charcoal hemoperfusion.

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.

Glycinergic neurotransmission is a major inhibitory influence in the CNS and its disruption triggers a paediatric and adult startle disorder, hyperekplexia. The postsynaptic α(1)-subunit (GLRA1) of the inhibitory glycine receptor (GlyR) and the cognate presynaptic glycine transporter (SLC6A5/GlyT2) are well-established genes of effect in hyperekplexia. Nevertheless, 52% of cases (117 from 232) remain gene negative and unexplained. Ligand-gated heteropentameric GlyRs form chloride ion channels that contain the α(1) and β-subunits (GLRB) in a 2α(1):3β configuration and they form the predominant population of GlyRs in the postnatal and adult human brain, brainstem and spinal cord. We screened GLRB through 117 GLRA1- and SLC6A5-negative hyperekplexia patients using a multiplex-polymerase chain reaction and Sanger sequencing approach. The screening identified recessive and dominant GLRB variants in 12 unrelated hyperekplexia probands. This primarily yielded homozygous null mutations, with nonsense (n = 3), small indel (n = 1), a large 95 kb deletion (n = 1), frameshifts (n = 1) and one recurrent splicing variant found in four cases. A further three cases were found with two homozygous and one dominant GLRB missense mutations. We provide strong evidence for the pathogenicity of GLRB mutations using splicing assays, deletion mapping, cell-surface biotinylation, expression studies and molecular modelling. This study describes the definitive assignment of GLRB as the third major gene for hyperekplexia and impacts on the genetic stratification and biological causation of this neonatal/paediatric disorder. Driven principally by consanguineous homozygosity of GLRB mutations, the study reveals long-term additive phenotypic outcomes for affected cases such as severe apnoea attacks, learning difficulties and developmental delay.

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.