Rangan Srinivasaraghavan

Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy.

Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-tyrosine catabolic pathway. We analysed DNA of 40 AKU patients enrolled for SONIA1, the first study in DevelopAKUre, and of 59 other AKU patients sent to our laboratory for molecular diagnostics. We identified 12 novel DNA variants: one was identified in patients from Brazil (c.557T>A), Slovakia (c.500C>T) and France (c.440T>C), three in patients from India (c.469+6T>C, c.650–85A>G, c.158G>A), and six in patients from Italy (c.742A>G, c.614G>A, c.1057A>C, c.752G>A, c.119A>C, c.926G>T). Thus, the total number of potential AKU-causing variants found in 380 patients reported in the HGD mutation database is now 129. Using mCSM and DUET, computational approaches based on the protein 3D structure, the novel missense variants are predicted to affect the activity of the enzyme by three mechanisms: decrease of stability of individual protomers, disruption of protomer-protomer interactions or modification of residues in the region of the active site. We also present an overview of AKU in Italy, where so far about 60 AKU cases are known and DNA analysis has been reported for 34 of them. In this rather small group, 26 different HGD variants affecting function were described, indicating rather high heterogeneity. Twelve of these variants seem to be specific for Italy.

Efficacy of scorpion antivenom plus prazosin versus prazosin alone for Mesobuthus tamulus scorpion sting envenomation in children: a randomised controlled trial

Objective To assess the efficacy of combined use of scorpion antivenom (SAV) with prazosin, compared with prazosin alone in children with Mesobuthus tamulus scorpion envenomation. Study design Randomised controlled trial. Setting A tertiary care hospital in south India. Patients 50 children with definite history and/or systemic manifestations of scorpion envenomation were recruited from the paediatric emergency or outpatient department from February 2012 to July 2013. Interventions The children were randomised into two groups. In 25 children, SAV was administrated as a slow intravenous bolus combined with prazosin (group A). Others received prazosin alone (group B). Results were analysed by Student t test and χ2 test. Main outcome measures Time required for resolution of autonomic symptoms, total dose of prazosin, adverse events. Results Children in group A recovered earlier than those in group B (mean difference 9.1 h, 95% CI 6.0 to 12.2). 23 children (92%) in group A were clear of autonomic symptoms within 10 h, compared with 10 children (40%) in group B (mean difference 52%, 95% CI 29% to 75%). The proportion of children deteriorating to clinical grade 3 or 4 was 8% in group A as against 44% in group B (p<0.01). The mean dose of prazosin required was 54 µg/kg versus 130.8 µg/kg in group A and B, respectively (p<0.01). SAV was not associated with severe adverse reactions. Conclusions Usage of SAV led to faster recovery and reduced the incidence of myocardial dysfunction. Combined therapy with SAV and prazosin is beneficial for children with M tamulus scorpion envenomation. Trial registration number: CTRI/2013/09/004002 (Clinical Trials Registry of India).

Acitretin‐Responsive Ichthyosis in Chanarin–Dorfman Syndrome with a Novel Mutation in the ABHD5/CGI‐58 Gene

Chanarin–Dorfman syndrome (CDS) is a rare nonlysosomal neutral lipid storage disorder characterized by congenital ichthyosis, lipid vacuoles in leukocytes (Jordans anomaly), and hepatomegaly. The authors herein report an 18‐month‐old boy with ichthyosis and hepatomegaly diagnosed with CDS and confirmed to have a novel c.506–3C>G mutation in the ABHD5/CGI‐58 gene. Our case also illustrates that retinoids such as acitretin could be useful in the treatment of skin manifestations in CDS even in the presence of liver derangement.

Predictors of Myocardial Dysfunction in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.

ObjectivesTo identify predictive risk factors for myocardial dysfunction in children with scorpion sting envenomation and to evaluate the effects of Scorpion antivenom and prazosin combination therapy on occurrence of myocardial dysfunction.DesignObservational.SettingTertiary care hospital in Southern India.Participants85 children aged < 13 years with scorpion sting envenomation.Outcome measuresFrequency of myocardial dysfunction; predictors of myocardial dysfunction.Results24 children (28.2%) developed myocardial dysfunction. Hypotension at admission (P=0.003) and increased time (>4h) between sting and administration of appropriate therapy (P=0.001) were independent predictors of myocardial dysfunction on logistic regression. Scorpion antivenom plus prazosin combination therapy led to an increase in cumulative proportion of children without myocardial dysfunction.ConclusionEarly (<4 hours) administration of Scorpion antivenom along with prazosin increases the cumulative percentage of children not developing myocardial dysfunction.

Is maternal anxiety a barrier to exclusive breastfeeding

Abstract Objective: To assess the association of maternal anxiety with nonadherence to exclusive breastfeeding. Methods: This questionnaire-based study was conducted at a tertiary care teaching hospital in South India mothers with infants less than 6 months of age and not exclusively breastfeeding were interviewed and their demographic and clinical details were noted. The Iowa Infant Feeding Attitude Scale (IIFAS) and Hospital Anxiety and Depression Scale (HADS) were administered to these mothers. Results: A total of 85 mother–infant dyads were included. The mean age of the mothers was 26 years and 57% were from urban areas. Among the additional feeds given, cow’s milk was the commonest (57.6%), followed by gripe water (28.2%) and formula feeds (16.5%). The mean HADS anxiety subscale score was 12.2 (±5.3) and HADS depression subscale score was 9.5 (±3.8). The mean score on IIFAS was 58.4 (±3.6) suggesting a relatively favorable attitude toward breastfeeding. On linear regression analysis, higher HADS depression score, lower birth weight and lower per capita income were independent predictors of poorer attitudes toward breastfeeding. Conclusion: Maternal anxiety may be an independent risk factor for nonadherence to exclusive breastfeeding for the initial six months.

Culture proven Salmonella typhi co-infection in a child with Dengue fever: a case report.

Infectious diseases are one of the major causes of morbidity and mortality in developing countries. Sometimes concurrent infections with multiple infectious agents may occur in one patient, which make the diagnosis and management a challenging task. The authors here present a case of co-infection of typhoid fever with dengue fever in a ten-year-old child and discuss the pertinent issues. The authors emphasize that the risk factors predicting the presence of such co-infections, if developed, will be immensely useful in areas where dengue outbreak occurs in the background of high transmission of endemic infections.

Catastrophic Intracranial Hemorrhage as a Presenting Feature of Juvenile Polyarteritis Nodosa

Intracranial hemorrhage has been rarely reported during the course of polyarteritis nodosa. We describe a 6-year-old boy who presented with fever, altered sensorium, skin rash, hypertension, and catastrophic intracranial hemorrhage. After surgical evacuation of the intracranial hematoma, he underwent a computerized tomography angiogram that showed narrowing of the right anterior cerebral artery. Skin biopsy showed small vessel vasculitis. Nerve conduction studies were suggestive of mononeuritis multiplex. He was diagnosed as polyarteritis nodosa and managed with immunosuppressants, to which he responded favorably. The most interesting aspect of the child’s presentation was the catastrophic onset of altered sensorium with raised intracranial pressure, which was a diagnostic challenge. The mechanisms of intracranial hemorrhage in polyarteritis nodosa and a review of the literature are discussed. The authors emphasize that it is important to recognize intracranial hemorrhage as a life-threatening complication in children with polyarteritis nodosa to institute timely therapy.

Impact of comorbidity on three month follow-up outcome of children with ADHD in a child guidance clinic: Preliminary report

Context: Attention deficit hyperactivity disorder (ADHD) is one of the common neurodevelopmental disorders. Aims: Study objective is to report impact of comorbidities on short-term outcome in children with ADHD followed in a child guidance clinic. Settings and Design: This was done in a child guidance clinic run jointly by the pediatric and psychiatry department at a tertiary teaching hospital. This is a 3 month prospective follow-up study to assess the outcome in ADHD children. Materials and Methods: Children attending pediatric department with behavioral problems or poor scholastic performance were screened for ADHD and further confirmation of diagnosis was done by semistructured interview of the child and parent. Children functional assessment and ADHD symptom profile was compared at baseline and at follow-up. We screened for and excluded those showing autistic spectrum disorder and having worse than mild mental retardation. Baseline variables were compared between improved and not improved subgroups and impact of these variables on outcome at 3-month follow-up was analyzed. Statistical Analysis: Descriptive statistics. Results: Of the 25 children completing the study, at the end of 3 months, 15 improved (not fulfilling criteria for ADHD) and 10 did not improve. Applying Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS) for diagnosis of psychiatric comorbidities, six had associated psychiatric comorbidities. This was significantly higher in those who did not improve. Conclusions: Presence of comorbidities at baseline was found to affect outcome at 3 month assessment in this preliminary study. Future studies with larger sample and longer follow-up are needed for finding the predictors of outcome in ADHD children in developing nations.

Antiquitin Deficiency with Adolescent Onset Epilepsy: Molecular Diagnosis in a Mother of Affected Offsprings

Antiquitin deficiency is the most prevalent form of pyridoxine-dependent epilepsy. While most patients present with neonatal onset of therapy-resistant seizures, a few cases with late-onset during infancy have been described. Here, we describe the juvenile onset of epilepsy at the age of 17 years due to antiquitin deficiency in an Indian female with homozygosity for the most prevalent ALDH7A1 missense mutation, c.1279G > C; p.Glu427Gln in exon 14. The diagnosis was established along familial cosegregation analysis for an affected offspring, that had neonatal pyridoxine responsive seizures and had been found to be compound heterozygous for c.1279G > C; p.Glu427Gln in exon 14 and a nonsense mutation c.796C > T; p.Arg266* in exon 9. While seizures in the mother had been incompletely controlled by levetiracetam, she remained seizure-free on pyridoxine monotherapy, 200 mg/day. Her fourth pregnancy resulted in a female affected offspring, who was treated prospectively and never developed seizures with a normal outcome at age 2 years while on pyridoxine. This report illustrates that the phenotypic spectrum of antiquitin deficiency is still underestimated and that this treatable inborn error of metabolism has to be considered in case of therapy-resistant seizures even at older age. It furthermore supports prospective in utero treatment with pyridoxine in forthcoming pregnancies at risk.

Prevalence of sub-clinical vitamin-D deficiency and hypothyroidism in children aged 18- 36 months with open anterior fontanelle: a cross-sectional study

The range of normal closure time of the anterior fontanelle (AF) is generally regarded to be 4 to 26 months. In one large study looking at time period for closure of anterior fontanelle, the closure was found to be 52.4% by 13 months of age, 78.6% by 16 months, and 95.6% by 19 months. The median time for closure is generally regarded as around 14 months. Many earlier researchers believed that AF closure is said to be delayed when it remains open beyond 18 months of age. The age of closure however varies depending upon race, sex and disease conditions. Some of the common causes for delayed AF closure include hypothyroidism, increased intracranial pressure, Down syndrome, achondroplasia, rickets, megalencephaly and normal variation. Before considering normal variation, it is important to rule out other common conditions mentioned above. In clinical practice, we do find a lot of normal children who have open AF well beyond 18 months without any tell-tale signs of any particular etiology. Therefore, one needs to use his or her judgement to decide whether a particular ABSTRACT