Identification of a Novel Homozygous Missense Mutation in the CLDN16 Gene to Decipher the Ambiguous Clinical Presentation Associated with Autosomal Dominant Hypocalcaemia and Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis in an Indian Family.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHNNC) is a rare autosomal recessive renal tubulopathy disorder characterized by excessive urinary loss of calcium and magnesium, polyuria, polydipsia, bilateral nephrocalcinosis, progressive chronic kidney disease, and renal failure. Also, sometimes amelogenesis imperfecta and severe ocular abnormalities are involved. The CLDN-16 and CLDN-19 genes encode the tight junction proteins claudin-16 and claudin-19, respectively, in the thick ascending loop of Henle in the kidney, epithelial cells of the retina, dental enamel, etc. Loss of function of the CLDN-16 and/or CLDN-19 genes leads to FHHNC. We present a case of FHHNC type 1, which was first confused with autosomal dominant hypocalcaemia (ADH) due to the presence of a very low serum parathyroid hormone (PTH) concentration and other similar clinical features before the genetic investigations. After the exome sequencing, FHHNC type 1 was confirmed by uncovering a novel homozygous missense mutation in the CLDN-16 gene (Exon 2, c.374 T > C) which causes, altered protein structure with F55S. Associated clinical, biochemical, and imaging findings also corroborate final diagnosis. Our findings expand the spectrum of the CLDN-16 mutation, which will further help in the genetic diagnosis and management of FHNNC.

Ten- vs. 14-day antibiotic therapy for culture-positive neonatal sepsis.

BACKGROUND: Neonatal sepsis is a major determinant of neonatal mortality. There is a scarcity of evidence-based guidelines for the duration of antibiotics in culture-positive sepsis. OBJECTIVES: The aim of this study was to compare the efficacy of 10- and 14-day antibiotic therapies in the management of culture-positive neonatal sepsis. METHODS: This randomized controlled trial was conducted in the neonatal intensive care unit of a tertiary care center among the neonates suffering from culture-positive sepsis (with signs of clinical remission on day 9 of antibiotic) between January 2023 and May 2023. Newborns with major congenital anomaly, deep-seated infections, multi-organ dysfunction, associated fungal infections/infection by multiple organisms and severe birth asphyxia were excluded. Two hundred and thirty-four newborns were randomized into two groups-study (received 10 days of antibiotics) and control (received 14 days of antibiotics). Treatment failure, hospital stay and adverse effects were compared between the two groups. p < 0.05 was taken as the limit of statistical significance. RESULTS: Median [interquartile range (IQR)] birth weight and gestational age of the study population (53.8% boys) were 2.424 kg (IQR: 2.183-2.695) and 37.3 weeks (IQR: 35.5-38.1), respectively. Acinetobacter was the most commonly isolated species (56, 23.9%). The baseline characteristics of both groups were almost similar. Treatment failure was similar in the study and control groups (3.8% vs. 1.7%, p = 0.40), with a shorter hospital stay [median (IQR): 14 (13-16) vs. 18 (17-19) days, p < 0.001]. CONCLUSION: Ten-day antibiotic therapy was comparable with 14-day antibiotic therapy in efficacy, with a shorter duration of hospital stay and without any significant increase in adverse effects.

Neonatal sepsis is a major cause of neonatal mortality in developing countries like India. Textbooks recommend 14-day antibiotic treatment for culture-positive neonatal sepsis. However, these guidelines are not strictly evidence based. Prolonged antibiotic treatment might be associated with drug resistance, secondary infections and organ damage. A shorter course of antibiotic, if found effective, would be beneficial especially in the resource-constrained settings like India. Hence, this study was undertaken to compare a shorter duration antibiotic treatment (10 days) with the conventional 14-day antibiotic therapy. Two hundred and thirty-four newborns with culture-positive sepsis were randomized into the study group (received 10 days of antibiotics) and the control group (received 14 days of antibiotics). Socio-demographic characters, clinical and laboratory features and bacteriological profile of both the groups were recorded. Both the groups were comparable in baseline features. Two-thirds of them were suffering from Gram-negative sepsis, Acinetobacter being the most commonly isolated organism. Incidence of treatment failure was similar in the study and control groups. Duration of hospital stay was significantly lower in the study group than in the control group. This observation was true irrespective of gestational age and type of organisms. There were no significant differences in adverse effects between the groups. However, there are certain limitations in the study, and hence, multi-centric research should be undertaken before making generalized recommendations of practising short duration of antibiotics.

Effect of deletions in the α-globin gene on the phenotype severity of ß-thalassemia.

Thalassemia is the most common inherited hemoglobinopathy worldwide. Variation of clinical symptoms in this hemoglobinopathy entails differences in disease-onset and transfusion requirements. The aim of this study was to investigate the role of α-globin gene deletions in modulating the clinical heterogeneity of ß-thalassemia (ß-thal) syndromes. A total number 270 ß-thal subjects were enrolled. Hematological parameters were recorded. ß-Globin mutations were determined by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR), gap-PCR and Sanger sequencing. α-Globin gene deletions were determined by multiplex PCR. Out of 270 ß-thal subjects, 19 carried ß+/ß+, 74 had ß0/ß0 and 177 had the ß0/ß+ genotype. When we determined the severity of the different ß-thal subjects in coinherited with the α gene deletion, it was revealed that, 84.2% ß+/ß+ subjects carried a non severe phenotype and did not have an α gene deletion. Of the ß0/ß0 individuals, 95.9% presented a severe phenotype, irrespective of α-globin gene deletions. In cases with the ß0/ß+ genotype, 19.2% subjects also carried a deletion on the α gene. Of these, 61.8% presented a non severe phenotype and 38.2% were severely affected. Only in the ß0/ß+ category did α gene deletions make a significant contribution (p < 0.001) toward alleviation of clinical severity. Therefore, it can be stated that α-globin gene deletions play a role in ameliorating the phenotype in patients with a ß+/ß0 genotype.

Serum (1,3)-b-D-Glucan for Screening of Neonatal Fungemia.

This study was conducted to identify the mycological pattern, and to calculate the diagnostic accuracy of serum (1,3)-b-D-glucan for screening fungal sepsis in 351 high-risk neonates. Candida tropicalis was the most common isolate (n=16, 38.1%). At optimum cut-off (47.2 pg/mL), sensitivity and specificity of serum (1,3)-b-D-glucan were 92.9% and 69.9%, respectively.

Clinical Profile and Short-Term Outcome of SARS-CoV-2-Infected Neonates from a Government Medical College in West Bengal, India.

INTRODUCTION: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to a terrifying global pandemic. The presentations in neonates are varied with less case severity compared to adults. AIM: To describe the clinical and laboratory features and outcomes of neonates admitted with SARS-CoV-2 infection during the second surge of COVID-19 pandemic in a Government Medical College, West Bengal, India. MATERIALS AND METHODS: It is a hospital-based observational cross-sectional study conducted in the newborn unit of Burdwan Medical College and Hospital between 1 April 2021 and 31 July 2021 including all SARS-CoV-2 Real time RT-PCR (Reverse transcriptase polymerase chain reaction) positive neonates. The demographic, clinical and laboratory characteristics of all the neonates and their outcomes were documented and analysed. RESULTS: Twenty-two neonates were found to be SARS-CoV-2 RT-PCR positive out of which 9 (40.9%) were found to be asymptomatic and 6 (27.27%) required neonatal intensive care unit admissions. Among the symptomatic neonates, most common presentations were respiratory distress (40.9%) and gastrointestinal manifestations (40.9%). Eight (36.36%) neonates required respiratory support. Three (13.6%) neonates had pneumonia of which one had right middle lobe collapse. Laboratory parameters were nonspecific except for the two (9%) cases of multisystem inflammatory syndrome in neonates. High-resolution computed tomography findings in two cases were suggestive of SARS-CoV-2 infection-induced changes. Two (9%) neonates died of which one was likely due to SARS-CoV-2 infection. CONCLUSION: Neonates with SARS-CoV-2 infection are mostly asymptomatic. However, clinicians must be vigilant as atypical presentations such as consolidation, collapse, meningitis or multisystem inflammatory syndrome may occur.

SARS-CoV-2 infection in neonates is rare with varied presentations ranging from asymptomatic neonates to a few presenting with multiorgan failure. The disease severity and case fatality are much less than in adults. We studied the clinical and laboratory features and outcomes of 22 neonates with SARS-CoV-2 infection during the second surge of COVID-19 pandemic. While nine (40.9%) neonates were asymptomatic, six (27.27%) required NICU admission. Pneumonia is a rare presentation in neonates but severe COVID-19 pneumonia resulting in consolidation and lobar collapse requiring positive pressure ventilation is a possibility. Multisystem inflammatory syndrome in neonates is also a clinical entity probably as a result of hyperinflammatory syndrome due to transplacental transfer of antibodies. They require rigorous treatment, close monitoring and regular follow-ups. Amniotic fluid, placental or cord blood testing is essential to ascertain the definite mode of transmission in these neonates.

Role of cooked green banana in home management of acute diarrhea in under-5 children.

BACKGROUND: Acute diarrhea is an important contributor to under-5 mortality. Green banana is traditionally used as a home-based remedy for diarrhea. OBJECTIVES: To identify the effect of green banana on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. METHODS: This study was conducted in the rural field practice area of a tertiary care center between January 2020 and December 2021 in under-5 children presenting with acute diarrhea with no/some dehydration. One hundred fifty-three children were divided into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Duration of diarrhea, proportion of children recovered, requirement of hospitalization, development of persistent diarrhea and number of diarrheal episodes in 1 year follow-up period were compared between two groups. RESULTS: Green banana supplementation was significantly associated with reduction in duration [median (interquartile range)-4 (1.5) day versus 5.5 (1) day, P < 0.001] of diarrhea, less hospitalization (9.2% versus 22.1%, P = 0.03) and early recovery, both at day 3 (17.1% versus 3.9%, P = 0.007) and day 7 (90.8% versus 77.9%, P = 0.03). Green banana also protected children from the development of persistent diarrhea (7.9% versus 19.5%, P = 0.04). It also reduced future episodes of diarrhea by 40.5%. CONCLUSION: Green banana supplementation could be a promising adjunct therapy in acute diarrhea and thereby it might reduce under-5 mortality.

Acute diarrhea is the second leading cause of under-5 mortality excluding neonatal causes in India where green banana has traditionally been used as a home-based remedy for diarrhea since ancient days. Some of the previous literatures have found promising results of green banana supplementation in prolonged diarrhea, dysentery and hospital management of acute diarrhea but none have considered it in the home management of diarrhea and have not reviewed its role on duration, recovery and prevention of severe dehydration in under-5 children with acute watery diarrhea with no/some dehydration. These issues along with the possible role of green banana in preventing future episodes of diarrhea have been addressed in our study. One hundred fifty-three under-5 children presenting with acute diarrhea with no/some dehydration were studied over 2 years dividing into group A (received cooked green banana supplementation along with standard management) and group B (received only standard management). Green banana supplementation was significantly associated with reduction in duration of diarrhea, less hospitalization and early recovery, lesser incidences of development of persistent diarrhea, and it also significantly reduced the future episodes of diarrhea. Hence, green banana could be a promising adjunct therapy in acute diarrhea and might reduce under-5 mortality.

Effect of Music on Outcomes of Birth Asphyxia: A Randomized Controlled Trial.

INTRODUCTION: Birth asphyxia may cause neuro-developmental impairment in the affected newborns especially those who had hypoxic-ischemic encephalopathy. Music therapy has been observed to help in reducing pain and stress in newborns and improve neurodevelopmental outcome. OBJECTIVES: The objective of this study is to determine the effects of music therapy on the outcomes of birth asphyxia. METHODS: A randomized controlled trial involving 3095 newborns born between January 2013 and August 2019 with birth asphyxia was conducted in the neonatal intensive care unit of Burdwan Medical College. They were distributed in two groups-A (received music therapy along with coventional management) and B (only received conventional management), using computer-generated randomization. Pain score was assessed during any painful procedure and the neurodevelopmental outcome was measured at 3rd, 6th, 12th, 18th and 24th months. p < 0.01 was considered statistically significant. RESULTS: A total of 3095 newborns were included with a mean gestation of 34.3 ± 2.1 weeks and 56.7% of them were male. Mean hospital stay, oxygen dependency, requirement of mechanical ventilation and incidence of apnea were significantly lesser among newborns of group A. Newborns of group B showed a significantly higher mean pain score, whereas newborns in Group A exhibited significantly greater mental and motor neurodevelopmental quotients. CONCLUSIONS: Music therapy was observed to help in reducing hospital stay, oxygen dependency, incidences of apnea, pain during procedures and also resulted in better neurodevelopmental outcome. However, before generalizing the findings, further multi-centric research should be undertaken.

The Prevalence of HBB Mutations among the Transfusion-Dependent and Non Transfusion-Dependent Hb E/ß-Thalassemia Children in a Tertiary Center of West Bengal, India.

Hb E (HBB: c.79G>A)/ß-thalassemia (Hb E/ß-thal) is responsible for nearly half of all the different kinds of severe ß-thal. This disorder is characterized by a wide range of clinical variability ranging from mild, asymptomatic non transfusion-dependent thalassemia (NTDT) to severe transfusion-dependent thalassemia (TDT). The aim of the present study was to determine the prevalence of different ß-globin gene (HBB) mutations in Hb E/ß-thal subjects and their potential role in transfusion dependence. One hundred and ten consecutive children with Hb E/ß-thal attending the Pediatric Department of Burdwan Medical College, Burdwan, West Bengal, India were enrolled. Based on hemoglobin (Hb) electrophoresis or high-performance liquid chromatography (HPLC), patients were recruited and later ß-globin gene sequencing was done to find out the prevalence of different HBB mutations. Transfusion-dependent thalassemia was seen in 42 children (38.2%), while NTDT was seen in 68 children (61.8%). A total of 10 different ß-globin mutant alleles were characterized. The most frequent mutation on the ß-globin gene was IVS-I-5 (G>C) (HBB: c0.92+5G>C) in both groups. The ß-globin gene mutations alone cannot determine transfusion dependence among the Hb E/ß-thal patients.

Implication of therapeutic outcomes associated with molecular characterization of paediatric aplastic anaemia.

OBJECTIVES: Severe aplastic anemia is characterized by a hypocellular bone marrow and peripheral cytopenia. Mesenchymal stem cells (MSCs) play a crucial role in haematopoietic stem cells (HSCs) development and the development of microenvironment suitable for hematopoiesis. Molecular characterization of telomere maintenance pathway and gene expression profiling of MSCs can be important for the therapeutic interventions among paediatric aplastic anaemia patients. METHODS: The study involved paediatric aplastic anaemia patients (n = 10) and age matched paediatric healthy donors (n = 8). Peripheral blood samples were collected from the individuals. Average leucocyte telomere length and gene expression of the telomere maintenance genes were determined by quantitative real time PCR. Microarray based gene expression profiles (GSE33812) of MSCs for five paediatric aplastic anaemia patients were analyzed compared to five healthy controls and the data was downloaded from the GEO database. RESULTS: The telomere length was significantly shorter among paediatric AA patients compared to age matched healthy donors. Interestingly, one subgroup (n = 2) of paediatric AA patients has moderate telomere length comparable to age matched healthy donors. Based on the gene expression analysis of telomere maintenance pathway, TERF2 was significantly downregulated among paediatric patients with shorter telomere length but not among paediatric patients with moderate telomere length. Gene expression profiling of MSCs revealed three differentially expressed genes (GAS2L3, MK167 and TMSB15A) among the patients and was associated with therapeutic outcome. CONCLUSION: Telomere length estimation and gene expression patterns of the MSCs and telomere length maintenance pathway may serve as a potential biomarker and could be associated with therapeutic choice of paediatric aplastic anaemia patients.

Nephritic syndrome following multiple bee stings: a late hypersensitivity reaction.

Most hypersensitivity reactions to insect stings are immediate, ranging from transient local reactions of little medical consequence to fatal anaphylaxis. Rarely, some patients have delayed reactions after a period of apparent normality which manifest as systemic features which can be life-threatening. A 3-year-old boy was attacked by a swarm of bees, estimated to be about 200 in number. There was an immediate cutaneous reaction which was treated at a local hospital. After 9 days, he presented with oliguria, dark-coloured urine, pedal oedema, hypertension and acute kidney injury (AKI). He was managed conservatively with fluid restriction, control of blood pressure and peritoneal dialysis, and renal function returned to normal gradually over the following 9 days. The delayed-onset AKI and other laboratory abnormalities suggested a immune-mediated type III hypersensitivity reaction leading to renal insufficiency. After improvement of initial hypersensitivity reactions, patients with bee stings should be followed up in order to detect any late-onset complications which might be life-threatening.

Prevalence of congenital anomalies in neonates and associated risk factors in a tertiary care hospital in eastern India.

BACKGROUND: Congenital anomalies are a major cause of stillbirths and neonatal mortality. The pattern and prevalence of congenital anomalies may vary over time or with geographical location. AIMS AND OBJECTIVES: The aim of this study is to determine the proportion and types of congenital anomalies in live newborns and to study maternal and perinatal risk factors. MATERIALS AND METHODS: This cross-sectional descriptive study was carried out in the neonatal care unit of R. G. Kar Medical College and Hospital during the period of September 2011 to August 2012. All the live born babies born in this hospital during this period were included. The newborns were examined for the presence of congenital anomalies and mothers were interviewed for socio-demographic variables. RESULTS: During the study period, 12,896 babies were born, of which 286 had congenital malformations, making the prevalence 2.22%. Most of the women (55.7%) belonged to the age group between 21 and 30 years. Congenital anomalies were seen more commonly (3.3%) in the multiparas in comparison with primiparas (1.8%). The predominant system involved was Musculo-skeletal system (33.2%) followed by gastro-intestinal (GI) system (15%). Talipes (17.1%) was the most common one in musculoskeletal group and likewise cleft lip and cleft palate in GI system. Congenital anomalies were more likely to be associated with low birth weight, prematurity, multiparity, consanguinity and cesarean delivery. CONCLUSION: Public awareness about preventable risk factors is to be created and early prenatal diagnosis and management of common anomalies is strongly recommended.

Umbilical myiasis in newborn.

Umbilical myiasis is rare in newborns. We are reporting two cases of umbilical myiasis from rural West Bengal (India) that were infected by larval forms of blow fly (Chrysomya megacephala). One of them subsequently developed septicemia while the other one was clinically well.

Lissencephaly--not an uncommon cause of intractable seizure in children: report of 3 cases.

Lissencephaly or azyria, a rare disorder characterised by the absence of cerebral convolutions and poorly formed sylvlan fissures giving the appearance of a foetal brain with smooth cerebral surface, thickened cortical mantle and microscopic appearance ofincomplete neuronal migration. It is to consider lissencephaly in the diagnosis of developmental delay with seizure disorder as many patients may be diagnosed as cerebral palsy. Several lissencephaly syndrome have been described, Here three cases of lissencephaly with developmental delay and Intractable seizures are reported.

Extragonadal teratomas presenting at birth and originating from 3 different sites--a report of 3 cases.

Three cases of extragonadal teratomas presented at birth and all the cases arisen from three separate sites are reported in the present study. A huge sacrococcygeal teratoma is being reported and the other two retroperitoneal and nasopharyngeal teratomas, are reported for the rarity of their location in neonatal period. Teratomas of all three babies were mature benign on histopathology and surgical removal sufficed as mode of treatment. No recurrence was noted on follow-up.

Holoprosencephaly--a case report.

A newborn female with delayed initiation of respiration was presented. She was born at term, normally of an uncomplicated pregnancy. Her head circumference was 40.5 cm. X-ray skull showed sutural separation. CT-scan of brain showed a large monoventricle occupying most of the cranial cavity. The case had typical features of albolar holoprosencephaly with hydrocephalus. The baby was treated for birth asphyxia.

Kluver-Bucy syndrome--a rare complication of herpes simplex encephalitis.

A twelve-year-old female was admitted with history of high fever, recurrent vomiting and repeated convulsion for 2 days and altered consciousness for one day. Cranial CT scan showed intraparenchymal haemorrhage involving both temporal lobes and right basal ganglia region without mass effect. Serology was reactive against IGM HSV1. Injection acyclovir was started at a dose of 10 mg/kg 8 hourly intravenously. Patient regained consciousness on fourth day but speech was altered. Abnormal behavioural symptoms were noticed. EEG showed generalised spike and slow waves and sharp and slow wave discharge more in the temporal region. The patient was given clonidine and carbamazepine. She also received behavioural therapy and parental counselling. She was followed up for six months and maintaining well.