Integrating health interventions in a growing economy like India, with a birth cohort of 27 million/year, one-fifth of all childbirths, and approximately one-third of neonatal deaths globally, is a challenge. While mortality statistics are vital, intact survival and early preventive healthcare, such as newborn screening (NBS), are paramount. The appalling lack of information about the precise burden of metabolic errors at the state/national level or a mandated program encouraged a feasibility study of NBS in a prospective newborn cohort recruited in Delhi State (November 2014–April 2017) using a public–private partnership mode. The major determinants for effective implementation of universal NBS at the national level and limitations encountered are discussed in this report. Data to generate the ‘core’ panel for screening, sustained training of healthcare personnel, dissemination of the power of NBS to ensure neonatal/societal health to the public, and a ‘national policy’ emerge as priorities in a developing country.

Symptomatic cytomegalovirus (CMV) infection mainly affects preterm and immunocompromised infants and usually manifest as rash, pneumonia, hepatospleenomegaly or encephalitis. To our knowledge intractable diarrhoea at two weeks of age caused by postnatally acquired CMV in immunocompetent term neonate is not reported. An unusual case of postnatally acquired CMV enterocolitis manifesting as protracted diarrhoea in an immunocompetent baby in neonatal period is reported. We conclude that CMV should be considered in the differential diagnosis of intractable diarrhoea in neonatal period and treatment with intravenous ganciclovir for CMV enterocolitis is not only indicated but is therapeutic.

Autoimmune disorders are increasingly recognized as a component of syndromic immune dysregulation, particularly in conditions with perturbed RAS/MAPK signaling such as Noonan syndrome. However, systematic evaluations of autoimmune antibody prevalence in Noonan Syndrome remain limited. In this two-year observational study (January 2021–December 2022) at a tertiary genetics center in New Delhi, 33 patients aged ≥3 years with clinically diagnosed NS (van der Burgt criteria) underwent phenotypic characterization, autoantibody profiling, and molecular analysis. Circulating autoantibodies for autoimmune thyroiditis, celiac disease, autoimmune hepatitis, and other connective tissue disorders were assessed using Line-Immuno Assay. Molecular testing included targeted Sanger sequencing for PTPN11, followed by next-generation sequencing in PTPN11-negative individuals. In this cohort, 30% (n=10) were autoantibody-positive, most commonly anti-TG (12%), anti-tTG IgA (9%), and anti-PM-Scl (9%), with a male predominance (60%) contrasting the usual female bias. Notably, no overt autoimmune disease was observed despite autoantibody positivity, except in one participant who had biopsy-proven celiac disease. Molecular analysis identified pathogenic or likely pathogenic variants in 82% (27/33) with PTPN11 as the predominant causative gene. Although a direct statistical correlation between genotype and autoantibody status was not established, a trend was observed wherein the majority of autoantibody-positive patients harbored PTPN11 variants. The findings highlight the need for longitudinal monitoring of autoantibody-positive NS individuals and suggest exploration of MAPK pathway modulation as a therapeutic strategy in syndromic autoimmunity.

Congenital hypothyroidism (CH) is a leading preventable cause of intellectual disability, with a notably high incidence in India. However, data integrating its morphologic and genetic etiology in Indian cohorts remain scarce. Aim of this study was to characterize its etiology via thyroid imaging to assess TSH levels across morphological sub-types and genetic analysis in a subset of the CH cases with dyshormonogenesis. In this multicentric prospective study, approximately 200,000 newborns (≥34 weeks) recruited from across 20 hospitals in Delhi state underwent TSH screening via heel prick. CH was confirmed by venous testing and managed with levothyroxine and etiological evaluation included thyroid ultrasonography and technetium scintigraphy. Dyshormonogenesis was the most common etiology (62%), followed by thyroid dysgenesis. Athyreosis showed the highest TSH levels and dyshormonogenesis had significantly lower values (p< 0.001). Male neonates exhibited greater skeletal maturation delay. Whole exome sequencing revealed monogenic (n=17) and digenic (n=7) inheritance in 24/41 samples (58.53%) of the dyshormonogenesis cases, with known and novel variants in reported genes and TG was the most frequently mutated gene. Integrating genetic, phenotypic, and functional data may enhance our understanding of CH and guide precision care.