Bhavna Dhingra

GM1 gangliosidosis is a rare, autosomal recessive, progressive, neurosomatic lysosomal storage disorder caused by GLB1 gene variants. The disease demonstrates significant phenotypic heterogeneity, with poor genotype-phenotype correlation. We describe a familial case series of five affected siblings presenting with a variable spectrum of disease manifestations. Clinical evaluation was performed in all siblings, whereas biochemical investigations and neuroimaging were performed in the proband and next-generation testing was performed in two severely affected sibling. Variant interpretation was carried out using standard American College of Medical Genetics and Genomics (ACMG) criteria and phenotype based re-annotation tool. Genetic testing identified compound heterozygous GLB1 variants - c.1325G > A and c.326G > C, confirming the diagnosis of GM1 gangliosidosis. Although the age of onset was similar (6-7 years) in most siblings, variability was observed in disease severity, neurological manifestations and progression. This series highlights the importance of molecular diagnosis in children presenting with unexplained neuroregression. Early genetic confirmation facilitates appropriate genetic counselling, supportive care and prenatal diagnosis.

Background: Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome is a rare autosomal recessive syndrome due to mutations in the claudin-1 gene (CLDN1). Defective expression of claudin-1 protein manifests with involvement of the liver and skin. Phenotypic expression of the disease varies from cholangitis resolving on supportive management to severe liver damage requiring liver transplantation. Case presentation: We hereby discuss an Indian infant presenting with neonatal cholestasis and ichthyosis, carrying a novel nonsense mutation in exon 3 of the CLDN1 gene (p.Pro154LeufsTer2). We also report a striking association between NISCH syndrome and hyperferritinemia; the pathophysiology for the same is yet to be elucidated. The patient’s clinical condition improved after supportive management, including vitamin supplementation, ursodeoxycholic acid, and emollients. Conclusion: Awareness, early diagnosis, genotype-phenotype correlation, and timely and appropriate management are key to the prognostication of the patient.

The most common cause of severe diarrhea in children under five is rotavirus infection. Pediatric comorbidities are integral components that may affect the prognostic outcomes of rotavirus gastroenteritis (RVGE). However, little is known about RVGE severity in the presence of comorbid conditions in children under five years of age. This study aims to compare the clinical outcomes of rotavirus diarrhea in children with and without co-morbidities. Children under five years of age suffering from acute diarrhea and admitted to the Inpatient Department (IPD)/Intensive Care Unit (ICU) were included. ELISA was used to identify the rotavirus antigen in stool samples obtained from each of the study participants. The Vesikari severity score index was used to assess the degree of disease severity. Out of the 76 participants recruited, rotavirus was detected in 13 (17.1%) cases. Comorbidities were present in 42 (55.2%) of the study participants, and eight (10.5%) patients had RVGE. The most common comorbidities observed were severe acute malnutrition (SAM) followed by malignancies. An increased frequency of diarrhea, vomiting, and fever was observed among children under five years of age with rotavirus diarrhea (p < 0.05). A significant difference in the severity of clinical manifestations was observed among RVGE patients with comorbidities (p < 0.05). This study demonstrated that rotavirus diarrhea was still common in hospitalized children under five years old, even though rotavirus vaccination was added to the universal immunization program. The presence of comorbidities further accelerated the deterioration of clinical conditions among RVGE patients highlighting the need for additional measures to prevent rotavirus infection in children with comorbid conditions.

India ranks among the top five countries in the world in child deaths due to pneumonia. Apart from poor public awareness, inadequate health infrastructure and treatment services have compromised effective management. This qualitative study guided by components of the Andersen-Newman’s health care utilization framework explored contextual and community challenges faced by health care providers (HCPs) in the delivery of care services for children with pneumonia in select districts of Uttar Pradesh (UP) and Madhya Pradesh (MP). Semi structured interviews (SSIs) and focus groups discussions (FGDs) were carried out with a purposive sample of HCPs selected from three districts in each state. The HCPs included doctors and community health workers (CHWs). All SSIs and FGDs were audio- recorded, with consent, transcribed verbatim, entered into NVivo and analysed using thematic analysis. A total of 15 SSIs were conducted with doctors and eight FGDs were carried out with CHWs. Two themes that best explained the data were:, 1. Health systems: barriers faced in delivery of care services and 2. Evaluated Need: perceptions on community awareness and practices. According to the HCPs inadequacies in government health infrastructure both manpower and equipment, and skill deficits of paramedical staff and CHWs contributed to poor quality of care services for management of childhood pneumonia. This combined with inadequate understanding of pneumonia in the community, dependence on unqualified care providers and distrust of government hospitals acted as barriers to seeking appropriate medical care. Additionally, poor compliance with exclusive breast feeding practices, nutrition and hygiene had contributed to the high prevalence of the disease in these states. Strengthening public health facilities, instilling trust and confidence in people about the availability and the quality of these services and enhancing health literacy around childhood pneumonia would be critical towards protecting children from this disease.

Background Children 0–14 years constitute about 31.4% of Indian population, among whom the magnitude and risk factors of childhood injuries have not been adequately studied. Objective To study the prevalence of and assess the factors associated with unintentional injuries among children aged 6 month–18 years in various regions. Methodology This multi-centric, cross-sectional, community-based study was conducted at 11 sites across India. States included were Gujarat, Karnataka, Madhya Pradesh, Punjab, Sikkim, Tamil Nadu, Uttarakhand, and West Bengal between March, 2018 and September, 2020. A total of 2341 urban and rural households from each site were selected based on probability proportionate to size. The World Health Organization (WHO) child injury questionnaire adapted to the Indian settings was used after validation. Information on injuries was collected for previous 12 months. Definitions for types (road traffic accidents, falls, burns, poisoning, drowning, animal-related injuries) and severity of injuries was adapted from the WHO study. Information was elicited from parents/primary caregivers. Data were collected electronically, and handled with a management information system. Results In the 25751 households studied, there were 31020 children aged 6 months–18 years. A total of 1452 children (66.1% males) had 1535 unintentional injuries (excluding minor injuries) had occurred in the preceding one year. The overall prevalence of unintentional injuries excluding minor injuries was 4.7% (95% CI: 4.4–4.9). The commonest type of injury was fall-related (842, 54.8%) and the least common was drowning (3, 0.2%). Injuries in the home environment accounted for more than 50% of cases. Conclusions The findings of the study provide inputs for developing a comprehensive child injury prevention policy in the country. Child safe school with age-appropriate measures, a safe home environment, and road safety measures for children should be a three-pronged approach in minimizing the number and the severity of child injuries both in urban and rural areas.