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.

Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child With G6PD Deficiency.

The authors herein report a 5-year-old child who presented with massive hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6-phosphate dehydrogenase deficiency with associated central nervous system symptoms probably because of concomitantly acquired methemoglobinemia following oxidant drug exposure. The associated acute-onset anemia would have contributed to the development of cerebral anoxia-related seizures and encephalopathy.

Immunoglobulin A nephropathy in association with generalized inflammatory peeling skin syndrome.

We describe an 8-year-old girl born to second-degree consanguineous parents with complaints of recurrent episodes of hematuria for 6 months. She had generalized peeling of the skin since birth and recurrent purulent cutaneous infections. The clinical presentation and histopathology of the skin biopsy specimen were consistent with the inflammatory variant of peeling skin syndrome (PSS). She also had a single ventricle with pulmonary stenosis, for which a bidirectional Glenn shunt had been placed. The renal biopsy specimen showed immunoglobulin A (IgA) nephropathy. She responded well to enalapril and steroids, with a decrease in proteinuria. IgA nephropathy has not been previously reported in PSS. Complications such as IgA nephropathy in children with PSS would help to further delineate the diverse clinical presentations and the clinical course of this rare dermatosis. We discuss the mechanisms that could explain this hitherto unreported association.

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 (Jordan's 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.

Structured early childhood education exposure and childhood cognition - Evidence from an Indian birth cohort.

Experiences in early childhood form the bedrock of future human potential. In impoverished settings, structured early childhood education (ECE) in preschool years can augment overall childhood and later human abilities. The current study evaluates preschool learning exposure and childhood cognition, using longitudinal follow-up of a community-based birth cohort in Vellore, south India. The birth cohort study site in Vellore recruited 251 newborns between 2010 and 2012 from dense urban settlements and further followed up into childhood. Preschool enrolment details were obtained from parents. Childhood cognition was assessed by Weschler's preschool primary scale of intelligence (WPPSI) and Malin's intelligence scale for Indian Children (MISIC) at 5 and 9 years of age respectively. Bivariate and multivariate regression analyses were performed with adjustments for socio-economic status (SES), maternal education, stunting status and home environment. Out of 251 new-borns recruited into the MAL-ED birth cohort, 212 (84.46%) and 205 (81.7%) children were available for the 5 year and 9 year follow-up respectively. At 5 years, structured ECE of 18 to 24 months duration was significantly associated with higher cognition scores, with the highest increase in processing speed [ß: 19.55 (11.26-27.77)], followed by full-scale intelligence [ß: 6.75 (2.96-10.550)], even after adjustments for SES, maternal cognition, home factors and early childhood stunting status. Similarly adjusted analysis at 9 years showed that children who attended 1.5-2 years of structured ECE persisted to have higher cognition, especially in the performance domain [ß: 8.82 (2.60-15.03)], followed by the full-scale intelligence [ß: 7.24 (2.52-11.90)]. Follow-up of an Indian birth cohort showed that structured ECE exposure was associated with better school entry cognition as well as mid-childhood cognition. Strengthening ECE through a multi-pronged approach could facilitate to maximize cognitive potential of human capital.

Vestibular stimulation with Indian hammock versus music intervention in the prevention of infantile colic in term infants: An open-labelled, randomized controlled trial.

BACKGROUND AND OBJECTIVES: To determine whether vestibular stimulation offered by Indian hammock and music intervention are useful in reducing the occurrence of infantile colic in term infants. METHODS: This open-labelled randomized clinical trial was conducted among 465 term neonates who were randomly assigned to one of three groups: music group, hammock group and control group. The music intervention was given for a cumulative duration of at least 4 h a day with one stretch of at least 1 h. In the hammock group, babies were put to sleep inside the Indian hammock and were swung gently until they sleep, and were allowed to sleep in it, until they wake up. For the control group, routine pre-discharge counselling was given. All parents were provided a cry log and were instructed to record the log of cry events and duration. The primary outcome measure was occurrence of infantile colic episode as defined by ROME IV criteria. The infants were followed up from birth until the age of 3.5 months, and the cry log was collected during each follow-up visit. RESULTS: Of the 435 term neonates who completed follow-up, 59 infants developed infantile colic (13.6%). The prevalence of infantile colic in the control group, music group and the Indian hammock group was 25.6%, 5.4% and 9.6% respectively; there was a significant reduction in the prevalence of infantile colic in the intervention groups as compared to the control group. CONCLUSIONS: Vestibular stimulation by Indian hammock and music intervention individually reduced the occurrence of infantile colic.

The Impact of Autism Spectrum Disorder in Comparison with Other Neuro-Developmental Disorders in Children on the Family: Single Centre Experience.

BACKGROUND: Neurodevelopmental disorders (NDD), especially autism spectrum disorder (ASD), have a substantial impact on the family, with a consequent decrease in the quality of life. The current study was undertaken to understand if having ASD contributed to a higher impact on families compared to other NDD and to understand additional factors impacting families of children with either disorder in a low-middle income country (LMIC) setting. METHODS: Impact of ASD and other NDD along with sociodemographic factors was examined, by a retrospective analysis, among 540 children in a tertiary care center in South India. RESULTS: Both ASD and NDD had high, but comparable, impact on the family. Being a girl child, having seizures, and having sleep problems predicted a higher impact. CONCLUSIONS: In children with NDD, managing co-morbidities such as achieving better seizure control and addressing sleep-related problems may improve the impact of NDD on the family. Gender disparity in disability needs to be studied within the local cultural context.

Is maternal anxiety a barrier to exclusive breastfeeding?

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.

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.

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.

Probiotic prophylaxis to prevent ventilator associated pneumonia (VAP) in children on mechanical ventilation: an open-label randomized controlled trial.

PURPOSE: Ventilator associated pneumonia (VAP) is one of the most common nosocomial infections in the pediatric intensive care unit (PICU). It is associated with increased mortality and prolonged hospital stay. Several preventive strategies have been introduced to reduce VAP. One novel intervention is prophylactic administration of probiotics. Studies on the effect of probiotics on VAP in pediatric populations are lacking. METHODS: This was an open-label randomized controlled trial. A total of 150 children no older than 12 years admitted to the PICU were recruited from November 2011 to July 2013. Children who were likely to require ventilation for more than 48 h were eligible for inclusion in the study. Patients were randomized into two groups after stratification based on age groups. Children in the intervention group received probiotic preparation twice a day beginning from the day of ICU admission till 7 days or discharge from ICU, whichever was earlier. The control group did not receive any placebo. Children were examined daily for evidence of VAP and were followed up till discharge from hospital. Incidence of VAP, duration of hospital stay, and mortality were compared. RESULTS: Children who received prophylactic probiotics had a lower incidence of VAP compared to the control group (17.1 % in the probiotics group vs 48.6 % in the control group, p < 0.001; 22 per 1,000 ventilated days vs 39 per 1,000 ventilated days, p = 0.02). On multiple logistic regression analysis, use of prophylactic probiotics decreased the incidence of VAP by 77 % and reduced the duration of ICU and hospital stays by an average of 2.1 and 3.3 days, respectively, after adjusting for the other confounders. No complications due to administration of probiotics were observed in the study. CONCLUSION: Prophylactic probiotics administration resulted in reduction of the incidence of VAP in critically ill children in a setting where baseline VAP rates are high. The intervention was found to be safe.

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

OBJECTIVE: To 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. DESIGN: Observational. SETTING: Tertiary care hospital in Southern India. PARTICIPANTS: 85 children aged <13 years with scorpion sting envenomation. OUTCOME MEASURES: Frequency of myocardial dysfunction; predictors of myocardial dysfunction. RESULTS: 24 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. CONCLUSIONS: Early (<4 hours) administration of Scorpion antivenom along with prazosin increases the cumulative percentage of children not developing myocardial dysfunction.

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.