High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Role of line probe assay in detection of Mycobacterium tuberculosis in children with pulmonary tuberculosis.

BACKGROUND: India is the highest TB burden country in the world with almost 27 lakh cases reported in 2019. Pediatric tuberculosis in India accounts for almost 31% of global TB burden. Despite such high mortality and morbidity in children, diagnosis of pulmonary TB in children still remains very challenging. MATERIAL AND METHODS: This cross-sectional study was conducted in a tertiary care hospital in Delhi, India. Children between 1 and 12 months with clinical suspicion of pulmonary tuberculosis who had not previously taken ATT were included. Early morning gastric aspirate samples were collected after overnight fasting, on two days. Both days sputum sample were subjected to sputum smear microscopy and one of the two samples was subjected to line probe assay (LPA), cartridge based nucleic acid amplification (CBNAAT) and mycobacterium growth in tube (MGIT-960). RESULTS: 84 children with pulmonary tuberculosis were enrolled. The most common presenting complaint was fever seen in 83 patients (98.8%). Only 17 (20.24%) were sputum smear positive by Ziehl- Neelsen (ZN) staining. LPA was positive in 47 (55.95%) samples and among these positive samples both INH and RIF resistance was detected in 2 (4.26%) samples. CBNAAT was positive in 53 patients (63%). Growth in liquid culture media (MGIT 960) was observed in 44 (52.38%) samples. Among 17 smear positive samples, LPA was detected in 14 (82.35%) samples and among 67 smear negative sample LPA was detected in 33 (49.25%) samples. LPA had 63.46% sensitivity, 100% specificity in detecting mycobacterium tuberculosis. DISCUSSION: WHO's recommendation for using LPAs has been limited to culture isolates or smear-positive sputum specimens. New data has since been generated on the use of LPAs as newer versions of LPA have been developed over past few years. Previous studies conducted using LPA version 1.0 reported much lower detection rate of mycobacterium tuberculosis in smear negative specimens. With the availability of newer versions such as Hain GenoTypeMTBDRplusversion 2 and Nipro NTM + MDRTB detection kit 2, the diagnostic utility of LPA may be enhanced.

Efficacy and Safety of Low Dose Insulin Infusion against Standard Dose Insulin Infusion in Children with Diabetic Ketoacidosis- An Open Labelled Randomized Controlled Trial.

Objective: To compare the efficacy and safety of low dose insulin infusion (0.05 U/kg/h) against the standard dose insulin infusion (0.1 U/kg/h) in children with diabetic ketoacidosis. Method: Children (age <12 years, n = 30) presenting with diabetic ketoacidosis were enrolled and randomised to receive insulin infusion either as 0.05 U/kg/h (low dose) or 0.1 U/kg/h (standard dose) as an open labelled randomised controlled trial. The rest of the management was identical in both groups. The time taken for resolution of acidosis (pH ≥7.3 and HCO3 ≥15) was the primary outcome variable. The secondary outcome variables included the time taken until a decline in blood glucose to 250 mg/dl, the proportion of children developing hypoglycemia and hypokalemia, and any treatment failure. Results: The two groups were similar with respect to mean age, weight and gender distribution. New-onset diabetes was diagnosed on 24/30. The mean ± SD time for resolution of acidosis was similar between the groups; 27.0 ± 6.1 hours in the low dose group vs 23.4 ± 7.3 hours in standard dose group, P = 0.16. The mean time for the decline in blood glucose to 250 mg/dl was 13.0 ± 5.9 hours in low dose vs 11.6 ± 6.0 hours in standard dose group, P = 0.52. A lesser proportion of participants developed hypoglycemia and hypokalemia in the low dose group, though not statistically significant. There was no incidence of treatment failure in either group. Conclusion: Low dose insulin infusion is equally effective and safe as standard dose insulin infusion in children with diabetic ketoacidosis.

Management of Obesity and Its Complications in Children and Adolescents.

Pediatric overweight/obesity has assumed epidemic proportions in India. It is associated with several significant complications and tracks into adulthood. The mainstay of management is a holistic lifestyle modification that must be adopted by the family as a whole. It involves dietary changes, regular physical activity, and behavioral changes that favor a healthy way of life. Regular follow-up, and attention to keeping up the motivation of the child and family achieves good results. In the present paper, a stepwise approach to prevention and management of childhood obesity is presented along with the recommendations for screening and management of associated complications and the role of pharmacotherapy and bariatric surgery.

Response to single oral dose vitamin D in obese vs non-obese vitamin D-deficient children.

Obese individuals are prone to vitamin D deficiency because of sequestration of vitamin D in their body fat. We planned to evaluate the rise in serum 25(OH)D levels in vitamin D-deficient obese vs normal body mass index(BMI) children, after administration of identical single dose of vitamin D. Twenty-two obese and 22 normal BMI children with serum 25 (OH)D < 20 ng/mL were given single oral dose 150,000 IU vitamin D, and 25 (OH)D levels were measured at 1 week and 1 month post-intervention. Results show that rise in 25(OH)D level from baseline was about 2.2 times lesser in obese compared with children with normal BMI, both at 1 week and at 1 month. The rise in 25(OH)D from baseline to 1 month was inversely correlated to BMI (r = - 0.56, p = < 0.001), waist circumference (r = - 0.48, p = 0.001), total fat mass (r = - 0.58, p < 0.001), and fat mass index (r = - 0.59, p < 0.001).Conclusion: The obese children have a 2.2 times lower rise in serum vitamin D levels as compared with the normal BMI children for the same dose of vitamin D supplementation. What is Known: • The obese individuals are prone to vitamin D deficiency and may be given higher doses of vitamin D supplementation. What is New: • Our study demonstrates that obese children have 2.2 times lesser rise in serum 25(OH)D concentrations as compared with normal BMI children when administered similar oral dose vitamin D.

Compromised Vitamin B12 Status of Indian Infants and Toddlers.

BACKGROUND: Vitamin B12 deficiency is prevalent worldwide especially in vegetarian communities. Its deficiency in early childhood may result in serious neurological and cognitive deficits. It is important to know the prevalence among our infants and toddlers so that nutritional policy changes could be suggested in this regard. OBJECTIVE: To evaluate the vitamin B12 status of apparently healthy Indian children between 6 and 23 months of age. METHODS: Apparently healthy Indian children (n = 210), of age 6 to 23 months, attending pediatric outpatient department were recruited and samples obtained to evaluate their hemogram and levels of vitamin B12, folate, and ferritin. Data were analyzed to obtain the mean levels and the proportion of participants deficient in vitamin B12. The dietary habits of the children were also analyzed and correlated with their vitamin B12 status. RESULTS: Vitamin B12 deficiency was observed in 37.6% of the participants. CONCLUSIONS: There is a high prevalence of vitamin B12 deficiency in our infants and toddlers, and there is need to initiate supplement to prevent any possible neurological consequences. Early initiation of animal milk had a positive effect on the vitamin B12 status of the child, though it was not significant.

Cytological diagnosis in a clinically unsuspected case of disseminated BCGosis: A case report.

Bacille Calmette-Guerin (BCG) vaccine is administered worldwide to neonates and considered safe. Serious complications like disseminated BCGosis are extremely rare occurrences (<1 per million vaccinations). A 6 months male was brought to paediatric outpatient department with fever and swelling over the dorsum of the left hand for 5 days. On examination, he was febrile and had hepatosplenomegaly. X-ray of the hand showed lytic lesions in the first and second metacarpals. Provisional clinical diagnosis included Langerhans cell histiocytosis, congenital syphilis, and haematological malignancy. Fine Needle Aspiration Cytology (FNAC) was done from the swelling and showed diffuse sheets of histiocytes with both intracellular and extracellular rod-shaped unstained structures along with inflammatory cells. These ghost images stained positive with ZN stain. A cytological diagnosis of atypical mycobacteria vs leprosy was made. Child was revisited and found to have an active BCG scar. Further investigations showed low serum IgM and positive AFB culture. These bacilli were confirmed by GenoType MTBDR plus test as Mycobacterium bovis. Despite Antitubercular therapy, the patient succumbed to death. This case highlights the variable clinical presentation of BCGosis. Its occurrence may unmask any underlying immunodeficiency. If unfamiliar with the above cytological features and in absence of routinely performed special stains, the cytopathologist may miss these notorious organisms and treat such cases like suppurative lesions. To conclude, an early and definitive diagnosis of BCGosis can be established on FNAC which would ensure timely management and better outcome in this highly lethal entity.

Efficacy and Safety of 90,000 IU versus 300,000 IU Single Dose Oral Vitamin D in Nutritional Rickets: A Randomized Controlled Trial.

AIM: To compare efficacy and safety of 90,000 IU versus 300,000 IU oral single dose vitamin D for treatment of nutritional rickets. STUDY DESIGN: Randomized controlled trial. SETTING: Tertiary care hospital. PARTICIPANTS: One hundred ten children (6 months to 5 years, median age 10.5 months) with rickets. Exclusion criteria were disease affecting absorption, intake of calcium/vitamin D preparation in last 6 months, abnormal renal function, and rickets other than nutritional. INTERVENTION: Vitamin D3 as a single oral dose 90,000 IU (group A, n = 55) or 300,000 IU (group B, n = 55). METHODOLOGY: Severity of rickets was scored on knee and wrist X-ray as per Thacher's radiographic score. Baseline serum levels of calcium, SAP, 25(OH)D, iPTH were measured. Follow up was done at 1 week, 4 weeks, and 12 weeks. OUTCOME VARIABLE: Primary - Radiographic score at 3 months. Secondary - Serum levels of 25(OH)D, SAP, and iPTH at 3 months, clinical and biochemical adverse effects. RESULTS: Eighty-six subjects (43 in each group) completed the study. The radiographic score reduced from 6.90 to 0.16 in group A and from 6.93 to 0.23 in group B. The levels of 25(OH)D, ALP, and PTH were similar between the groups at baseline and follow up. Hypercalciuria and hypercalcemia were seen more often in group B as was hypervitaminosis D. There were no clinical adverse events. CONCLUSIONS: Single oral dose vitamin D3 90,000 IU is safe and effective in achieving healing of rickets.

Designing and Validation of a Hindi-language Parent Self-report Developmental Screening Tool.

AIM: To design and validate Hindi-language parent self-report developmental screening questionnaires for 9-month and 18-month-old Indian children. DESIGN: Cross-sectional study. SETTING: Tertiary-care pediatric hospital from April 2014 to March 2016. PARTICIPANTS: In each age group (9-month and 18-month), 45 children were enrolled for designing of questionnaires (30 for obtaining parental observations of current development and 15 for pre-testing). For validation of tool, 100 children (60 low risk and 40 high risk) were enrolled in each age group. METHODS: For designing, observations regarding current developmental milestones were obtained from parents and a list of all enumerated milestones was prepared. After detailed discussion by a team of developmental pediatricians, pediatric resident, clinical psychologist and language specialist, milestones were chosen for drafting of questionnaires. In each age group, drafts were pre-tested and required modifications were done. The final questionnaires contained 20 items each to be scored on a Likert scale (total score ranging from 20 to 60, a lower score indicating a higher risk of developmental delay). These questionnaires were validated against Developmental Assessment Scale for Indian Infants (DASII), a gold standard instrument. RESULTS: On ROC analysis, the 9-month and 18-month screening tool had area under curve of 0.988 and 0.953, respectively, for detecting developmental delay. Score ≤50 on the 9-months questionnaire had sensitivity of 100% and specificity of 87.2%. Score ≤49 on the 18-months questionnaire had sensitivity of 91.4% and specificity of 88.7%. CONCLUSION: The new questionnaires have a promising role in developmental screening of children at the time of routine immunizations in our country.

Perturbing Status of Vitamin B12 in Indian Infants and Their Mothers.

BACKGROUND: Vitamin B12 deficiency in early life can adversely affect the growth of developing brain with myriad of neurodevelopmental manifestations. At this age, the deficiency is usually the result of low maternal levels. OBJECTIVES: To assess the vitamin B12 status of healthy exclusively breast-fed Indian infants aged 1 to 6 months and their mothers. METHODS: One hundred term exclusively breast-fed infants aged 1 to 6 months attending pediatric outpatient department were recruited. Hemogram, serum B12, folate, and ferritin levels were obtained from each infant-mother pair. RESULTS: The prevalence of B12 deficiency in infants was found to be 57%. Forty-six percent of mothers were deficient. There was a positive correlation ( r = .23) between the B12 levels of the infants and their mothers. CONCLUSION: There is a high prevalence of vitamin B12 deficiency in Indian infants and their mothers. There is an urgent need to supplement our population with vitamin B12, and the best time to do this would be antenatal.

Inadvertent Massive Overdose of Lidocaine in an Infant With Arthrogryposis Multiplex Congenita Treated Successfully With Lipid Emulsion.

Severe local anesthetic toxicity is potentially life threatening and is often refractory to standard resuscitative measures. Infants are a particularly susceptible population in this regard because of their unique physiologic features. Recently, 20% intravenous (IV) lipid emulsion (Intralipid) has been proposed as a "one-stop solution" to toxicity related to all commonly used amide local anesthetics. There is an abundance of literature describing its uses in association with regional blocks in adults. However, there is a scarcity of reports describing its application in children, and use of 10% IV lipid emulsion (Intralipid) has not been described in children for rescue therapy, to our knowledge. We report a case of accidental life-threatening overdose of IV lidocaine (lignocaine) in an infant, which was successfully managed with 10% lipid emulsion.

Delayed Diagnosis of Dopa responsive Dystonia in Two Siblings.

BACKGROUND: Dopa responsive dystonia is characterized by progressive disabling dystonia, diurnal variation and a dramatic response to Levodopa. CASE CHARACTERISTICS: Two siblings presented with regression of motor milestones and hypertonia in lower limbs. History of diurnal variation was present in elder sibling. OUTCOME: Both responded dramatically to Levodopa. The genomic DNA analysis of elder sibling revealed a novel mutation. MESSAGE: A trial of Levodopa should be considered in a child with motor regression with diurnal variation, in the presence of extrapyramidal features.

Vitamin B12 deficiency in children: a treatable cause of neurodevelopmental delay.

Vitamin B12 deficiency in children can rarely cause neurologic manifestations. In this series, 14 pediatric cases (median age 11 months) have been described in whom association of vitamin B12 deficiency with developmental delay or regression was observed. Severe to profound delay was present in 8 (57%) patients. All the patients were exclusively or predominantly breast-fed and 10 of 12 mothers had low serum vitamin B12 levels. Three to 6 months after treatment, a mean gain of development quotient of 38.8 points was seen in 7 follow-ups. In settings with a high prevalence of vitamin B12 deficiency, this association should be actively searched for.

Large multifocal cutaneous hemangioma along lines of Blaschko with cardiac failure treated with propranolol.

Hemangiomas are classified as focal or segmental according to the morphology and distribution of lesions. Congestive cardiac failure is frequently encountered in diffuse hepatic hemangiomas due to high-volume shunting and rarely in hemangiomas confined to the skin. We report here the case of a large multifocal hemangioma along the lines of Blaschko with high-output cardiac failure, with improvement in cutaneous and hemodynamic symptoms after propranolol therapy. Presentation along the lines of Blaschko raises the possibility of hemangiomas arising as a result of mosaicism.

Emerging new trends of malaria in children: a study from a tertiary care centre in northern India.

BACKGROUND & OBJECTIVES: Vivax malaria has long been considered a benign entity. However, an increasing number of reports are highlighting that it may no longer be so. An investigation was carried out to study the profile of malarial admissions in a tertiary care pediatric hospital and to analyse the burden of vivax-related complications. METHODS: It is a retrospective observational study. The medical case records of all the patients admitted in the year 2011 with the clinical diagnosis of malaria and laboratory evidence in the form of positive peripheral smear and/or rapid malarial antigen test were retrieved and retrospectively analysed. RESULTS: Overall, 198 cases were included, 128 (64.6%) were due to Plasmodium vivax, 66 (33.3%) due to P. falciparum and 4 (2%) had evidence of mixed infection of Pv + Pf. The clinical features on admission were similar in all the groups. In total, 64/128 (50%) patients with vivax infection had one or more complications with severe anemia in 33 (26%) and cerebral malaria in 16 (12.5%). Six deaths were reported in P. vivax cases. In the falciparum group, 52 (78.8%) had one or more complications with severe anemia in 37 (56.1%) and cerebral malaria in 24 (36.4%). Four deaths were reported in P. falciparum cases. INTERPRETATION & CONCLUSION: Overall because of their larger numbers, vivax patients outnumbered other groups, with regards to severe complications and deaths. It was concluded that vivax malaria is emerging as an important cause of malaria-related complications in children.