Beta-thalassemia and the advent of new interventions beyond transfusion and iron chelation.

Beta-thalassaemia, including sickle cell anaemia and thalassaemia E, is most common in developing countries in tropical and subtropic regions. Because carriers have migrated there owing to demographic migration, ß-thalassaemia can now be detected in areas other than malaria-endemic areas. Every year, an estimated 300 000-500 000 infants, the vast majority of whom are from developing countries, are born with a severe haemoglobin anomaly. Currently, some basic techniques, which include iron chelation therapy, hydroxyurea, blood transfusion, splenectomy and haematopoietic stem cell transplantation, are being used to manage thalassaemia patients. Despite being the backbone of treatment, traditional techniques have several drawbacks and limitations. Ineffective erythropoiesis, correction of globin chain imbalance and adjustment of iron metabolism are some of the innovative treatment methods that have been developed in the care of thalassaemia patients in recent years. Moreover, regulating the expression of B-cell lymphoma/leukaemia 11A and sex-determining region Y-box through the enhanced expression of micro RNAs can also be considered putative targets for managing haemoglobinopathies. This review focuses on the biological basis of ß-globin gene production, the pathophysiology of ß-thalassaemia and the treatment options that have recently been introduced.

Hypertensive encephalopathy following snake bite in a child: A diagnostic dilemma.

Children in rural India are a vulnerable group for snake bites. Improper elicitation of history and atypical presentations could lead to misdiagnosis and delay in treatment. We are reporting the case of an 8-year-old male child who presented with convulsions, unconsciousness and hypertension who was initially managed as a case of hypertensive encephalopathy showing no sign of improvement even after 20 hs. The history when reviewed suggested neurotoxic snake bite although the patient did not have any classical local findings. Anti-snake venom administration was followed by prompt recovery. We therefore suggest that snake bite should be considered in patients from rural background presenting with hypertension, convulsion and unconsciousness, even in the absence of classical features of snake bite.

Direct sequencing of ß-globin gene reveals a rare combination of two exonic and two intronic variants in a ß-thalassemia major patient: a case report.

BACKGROUND: Due to indels in the ß-globin gene, patients with ß-thalassemia major exhibit a range of severity, with genotype ß0ß0 > ß0ß+ > ß+ß+, according to the production level of the ß-globin chain. More than 300 mutations have been identified in the ß-globin gene. CASE PRESENTATION: In this case study, we report a compound heterozygous condition with a rare concoction of four different variants (CD 3(T > C), CD41/42 (-CTTT), IVS II-16 (G > C), and IVS II-666 (C > T) in a single ß-globin gene. A regular transfusion-dependent 4-year-old male patient from India was included in the study. Augmented direct sequencing of the ß-globin gene helped reveal the presence of an unusual combination of different variants in a single gene. This patient clinically presented as ß-thalassemia major and was genotypically considered as ß0ß+, although CD41/42(-CTTT) was the only causative/pathogenic mutation in the disease severity. CONCLUSION: Although CD41/42-(CTTT) is the only pathogenic variant among the four variants, the clinical complications of such a combination of variants (pathogenic and benign) is not well understood. Intronic mutations may have the ability to modify clinical characteristics. The variants must therefore be reclassified using additional mRNA splicing and expression-based studies. Additionally, these types of combinations may have significance in studying population migration around the world.

A Novel Frameshift Mutation, Deletion of HBB:c.199_202delAAAG [Codon 66/67 (-AAAG)] in ß-Thalassemia Major Patients from the Western Region of Uttar Pradesh, India.

PURPOSE: Beta thalassemia is one of the most common inherited disorders in India with heterogenous clinical phenotypes from silent carrier to clinically severe ones. Our study aimed to characterize the mutation spectrum in thalassemia patients who are coming to the hospital for follow-up from the western region of Uttar Pradesh India. PATIENTS AND METHODS: For the study, a case series of the retrospective bi-centre study was conducted. The patients from two thalassemia centers in the major hospitals (LLRMC Meerut, and JNMC, Aligarh administered by the Ministry of Health and Family Welfare (MoHFW)) in the Western Uttar Pradesh, India were considered for the study. A total of 77 blood samples were obtained from individuals (both related and unrelated) diagnosed with ß-thalassemia after their consent. After DNA extraction, HBB gene amplification, mutation-specific polymerase chain reaction and gene sequencing were carried out to analyze the mutations. RESULTS: In this study, seven different types of mutations were reported for the first time in Western Uttar Pradesh, India. A novel frameshift mutation, deletion of 4 nucleotides Codon 66/67 (-AAAG) in exon 2 region, is reported for the first time. IVS 1-5 (G>C) and Codon 41/42 (-CTTT) are the most frequently reported mutations. The molecular spectrum for these two cases consists of 44 and 42 alleles out of 108 alleles, respectively. CONCLUSION: A total of 108 ß-thalassemia alleles were studied from 46 homozygous and 31 compound heterozygous patients. All the individuals were from 20 districts of the Western Uttar Pradesh, India.

Frequency of HIV infection amongst children with disseminated tuberculosis and tuberculous meningitis in Aligarh (North India) - a low HIV prevalence area.

OBJECTIVE: To determine frequency of HIV in children with disseminated tuberculosis and tuberculous meningitis in a low HIV prevalence area, and to study clinical profile of those found HIV positive. STUDY DESIGN: Cross-sectional, descriptive study. PLACE AND DURATION OF STUDY: Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India from February 2005 to January 2008. METHODOLOGY: The study was conducted on 215 children under 14 years of age with either disseminated tuberculosis or tuberculous meningitis. HIV infection was diagnosed in accordance with WHO strategy II. In children younger than 18 months, the strategy (to cut down costs) was to screen first by HIV antibody testing and subject only positive cases to virological tests. Parents of HIV positive children were also tested for HIV and counselled. The clinical profile of HIV positive patients was noted. RESULTS: The frequency of HIV was 5.12%, while that in cases of disseminated tuberculosis was much higher (22%). No case with isolated tuberculous meningitis was HIV positive. The majority (45.45%) of patients with HIV were between 1-5 years of age. The mode of infection in 7 (63.63%) cases was parent to child transmission. Loss of weight, prolonged fever, pallor, hepato-splenomegaly and oral candidiasis were the commonest clinical manifestations among HIV positive patients. CONCLUSION: Clinically directed selective HIV screening in cases of disseminated tuberculosis can pickup undiagnosed cases of the same in areas with low prevalence of HIV infection.

Rickets in a 6-year-old girl resulting in extreme deformities.

Rickets remains endemic in low- and middle-income countries (LMIC) and has re-emerged in high-income countries. Poverty, ignorance and poor healthcare in LMIC still contribute to development of the disease and, if untreated, its progression to severe forms. A 6-year-old girl from a poor background presented with malnutrition, anaemia, rachitic rosary and severe deformities of the upper and lower limbs owing to vitamin D deficiency. Although she responded well to treatment initially, some of the deformities required surgical intervention. Unfortunately, she was lost to follow-up.

Effect of Oral Iron on Markers of Oxidative Stress and Antioxidant Status in Children with Iron Deficiency Anaemia.

INTRODUCTION: Conflicting reports are available on the relationship of Iron Deficiency Anaemia (IDA) and iron therapy with oxidative stress. AIM: To study the levels of markers of oxidative stress and anti-oxidant status in children with IDA and to assess the effect of iron therapy on the same. MATERIALS AND METHODS: This prospective, single centre, hospital based study was a sub-study of a randomized controlled trial conducted in the Department of Paediatrics, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh in collaboration with the Department of Biochemistry (of the same institution) between October 2009 to February 2011. The sub-study was conducted in two parts: in the first part, levels of a biomarker of oxidative stress {Malondialdehyde (MDA)} and anti-oxidant enzymes {Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx)} were assessed and compared between 67 children with IDA and 31 non-anaemic controls; in the second part, the effect of oral iron (6mg/kg/day) for eight weeks on these markers was studied in a subset of 35 children with IDA. The Bivariate correlations procedure was used to compute pair wise associations for a set of variables. T-tests (Independent samples t-test/Paired sample t-test) and Non-parametric tests (Mann-Whitney test/Wilcoxon signed-rank test) were applied as applicable for normally and non-normally distributed data, respectively. RESULTS: Levels of anti-oxidant enzymes were significantly lower (p<0.001) in children with IDA as compared to controls, viz., SOD {median, 8.63 (IQR, 8.60-8.66) vs. 9.46 (IQR, 9.14-9.62) units/mg protein}, CAT {median, 8.49 (IQR, 8.46-8.50) vs. 9.10 (IQR, 9.04-9.14) µmol H2O2/min/mg protein} and GPx {median, 49.19 (IQR, 48.99-49.60) vs. 56.94(IQR, 56.80-57.14) mol NADPH oxidized /min/ mg protein}. Whereas, levels of MDA were significantly higher (p<0.001) in IDA group {median, 1.50 (IQR, 1.48-1.52) vs. 1.24 (IQR, 1.20-1.27) moles/ml of serum}. Levels of Haemoglobin (Hb) and markers of iron status (serum iron, transferrin saturation and ferritin) had a very strong, highly significant positive correlation (p<0.001) with levels of anti-oxidant enzymes (SOD, CAT, and GPx) but a very strong, highly significant negative correlation (p<0.001) with MDA. Total Iron Binding Capacity (TIBC) on the other hand, had a strong, highly significant (p<0.001) negative correlation with SOD, CAT, and GPx but a strong, highly significant positive correlation (p<0.001) with MDA. After eight weeks of daily iron therapy, a highly significant rise (p<0.001) from baseline was observed in levels of SOD, CAT, and GPx in subjects with IDA. On the other hand, MDA levels declined significantly (p<0.001). CONCLUSION: Lipid peroxidation is increased and anti-oxidant defenses lowered in IDA. These changes, however, may be mitigated effectively with oral iron therapy.

Infant and Young Child Feeding Guidelines, 2016.

JUSTIFICATION: Shaping up the post-2015 development agenda is of crucial importance in the development process around the Globe as 2015 was the last year of milllionium development goals. It is the right time to asses our own progress vis-a-vis the Millennium Development Goals and these Guidelines are an attempt in that regard. PROCESS: The Infant and Young Child Feeding (IYCF) chapter of Indian Academy of Pediatrics invited a group of experts for National Consultative Meet for discussing and contributing on latest scientific advances and developments. Various partners from WHO, UNICEF, Ministry of Child Welfare Department, Ministry of Health and Family Welfare, Ministry of Chemical and Fertilizers of Govt of India, Human Milk Banking Association (of India), Indian Medico-Legal and Ethics Association (IMLEA), non-governmental organizations and academicians from various states of India contributed to these guidelines. The guidelines were finalized during the IYCNCON 2015 at New Delhi in August 2015. OBJECTIVES: To formulate, endorse, adopt and disseminate guidelines related to Infant and Young Child feeding from an Indian perspective (including human milk banking, infant feeding in the HIV situation, and micro-nutrients). RECOMMENDATIONS: Early initiation of breastfeeding within first hour of birth, exclusive breastfeeding for the first six months followed by continued breastfeeding for up to two years and beyond with appropriate complementary foods after completion of 6 months is the most appropriate feeding strategy. Micro-nutrient supplementation in infants, and adequate nutrition and anemia control for adolescent girls, pregnant and lactating mothers is advocated. Concepts and need for human milk banks in India has also been incorporated.

Embryonal Carcinoma in Cryptorchid Abdominal Testis of an Infant.

Cryptorchidism is a known predisposing factor for the development of testicular tumors in adults. Age of patient at the time of treatment of undescended testes has some bearing on the risk of neoplasia. Testicular neoplasia at the time of primary surgery for cryptorchidism has been reported rarely in prepubertal period. We report a case where embryonal carcinoma was detected in a cryptorchid testis of an infant.

Effect of short term zinc supplementation on iron status of children with acute diarrhea.

OBJECTIVE: To study the effect of short term (2 wk) zinc supplementation on hemoglobin and iron status of children with acute diarrhea. METHODS: This study was a prospective, open label, single arm interventional trial conducted from June 2008 through October 2009 in a teaching hospital of North India. Three to sixty months old children presenting with acute diarrhea participated in the study. Subjects were supplemented with recommended doses of oral zinc gluconate for 2 wk. Changes in levels of hemoglobin, serum iron, total iron binding capacity, and serum ferritin were the main outcome measures. RESULTS: Sixty-two patients completed the study successfully. The prevalence of anemia before and after 2 wk of zinc supplementation remained unchanged. However, a small decline (p > 0.05) was observed in mean hemoglobin (from 8.95 ± 1.4 to 8.73 ± 1.43 g/dL), serum iron (79.56 ± 45.81 to 78.61 ± 44.41 µg/dL) and ferritin (84.77 ± 45.35 to 83.55 ± 44.10 ng/mL) levels. Total iron binding capacity increased from 331.60 ± 109.72 to 341.30 ± 119.90 µg/dL post supplementation (p > 0.05). CONCLUSIONS: Even though statistically insignificant, the small change observed in the levels of hemoglobin, and indicators of iron status following short term zinc supplementation might assume significance in some settings in developing countries where children receive short courses of zinc repeatedly for frequent diarrheal episodes.

Evaluation of salivary anti-Salmonella typhi lipopolysaccharide IgA ELISA for serodiagnosis of typhoid fever in children.

This observational study was conducted to determine the diagnostic accuracy of ELISA for the detection of anti-Salmonella typhi lipopolysaccharide (LPS) salivary immunoglobulin A (IgA) antibodies in 37 children with culture confirmed typhoid, 30 febrile controls with an alternative diagnosis and 30 healthy controls. The test was positive in 33/37 (89.2%) cases of typhoid, but negative in all patients in the two control groups. Maximum absorbance of anti-LPS IgA was observed during the second and third weeks of typhoid, with a progressive decline thereafter. The sensitivity of ELISA was 71.4%, 100%, 100%, 9.1% and 0%, in first, second, third, fourth and fifth week of illness, respectively. Further large scale studies measuring salivary anti-LPS IgA antibodies are needed to confirm the potential of saliva-based serology in children with suspected typhoid.

Cholangitis and choledocholithiasis after repair of duodenal atresia: a case report.

Cholelithiasis is a rare but known complication of surgery for duodenal atresia. Occurrence of choledocholithiasis as sequelae of duodenoduodenostomy is still rarer. Biliary stasis resulting from compression of common bile duct due to periductal fibrosis may predispose to gallstone formation. We are reporting a case of choledocholithiasis in a 6 year old child as a late post-operative complication of duodenoduodenostomy (for duodenal atresia in the neonatal period). To the best of our knowledge this is the first case of its kind reported in English literature. Cholecystectomy followed by choledocholithotomy was done and the patient had an uneventful recovery. Upper abdominal pain in any patient with a history of surgery for duodenal atresia in the past warrants a thorough evaluation for any biliary tract anomaly, cholecystitis, cholangitis, cholelithiasis or choledocholithiasis.