Primary immunodeficiency (PID) refers to a group of heterogeneous genetic disorders with a weakened immune system. Mendelian susceptibility to mycobacterial disease (MSMD) is a subset of PID in which patients exhibit defects in intrinsic and innate immunity. It is a rare congenital disorder characterized by severe and recurrent infections caused by weakly virulent mycobacteria or other environmental mycobacteria. Any delay in definitive diagnosis poses a major concern due to the confounding nature of infections and immune deficiencies. Here, we report the clinical, immunological, and genetic characteristics of two siblings (infants) with recurrent infections. There was a history of death of two other siblings in the family after BCG vaccination. Whole exome sequencing of the two affected surviving infants along with their consanguineous parents identified a novel, homozygous single nucleotide splice acceptor site variant in intron 2 of the interferon gamma receptor 2 ( IFNGR2 ) gene. Sanger sequencing of DNA obtained from blood and fibroblasts confirmed the variant. The patients underwent bone marrow transplantation from their father as a donor. RT-PCR and Sanger sequencing of the cDNA of patients from blood samples after transplantation showed the expression of both wild type and mutant transcript expression of IFNGR2 . To assess partial or complete expression of IFNGR2 mutant transcripts, fibroblasts were cultured from skin biopsies. RT-PCR and Sanger sequencing of cDNA obtained from patient fibroblasts revealed complete expression of mutant allele and acquisition of a cryptic splice acceptor site in exon 3 that resulted in deletion of 9 nucleotides in exon 3. This led to an in-frame deletion of three amino acids p.(Thr70-Ser72) located in a fibronectin type III (FN3) domain in the extracellular region of IFNGR2. This illustrates individualized medicine enabled by next generation sequencing as identification of this mutation helped in the clinical diagnosis of MSMD in the infants as well as in choosing the most appropriate therapeutic option.

PURPOSE The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software. PATIENTS AND METHODS These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis. RESULTS The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss ( P = .01), renal dysfunction ( P = .047), and anemia at diagnosis ( P = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, P = .049), 3.18 (1.39-7.29, P = .0063), and 2.81 (1.22-6.42, P = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, P = .046). CONCLUSION The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.

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Background The native population of the Ladakh region faces the unique challenges of a high-altitude environment with distinct physiological adaptations in comparison with lowlanders. However, no comprehensive data on standard anthropometric parameters for the school-going children in this populace is available. Objectives We aimed to study the various anthropometric parameters in the school-going native highlander population and computed measures of central tendency. The nutritional status of the community was also be determined by comparing with World Health Organization (WHO) scores for height for age (HFA), weight for age (WFA) and body mass index (BMI) for age. Design A cross-sectional, descriptive study was devised to assess the anthropometric parameters. We measured height, weight, mid-upper circumference (MUAC), triceps skinfold (TSF) thickness, sub-scapular skinfold (SSF) thickness, waist, hip and abdominal circumference. Statistical analysis was conducted to determine the mean [±2 standard deviation (SD)], median, range, minimum and maximum. The z-scores for HFA, WFA and BMI for age was computed using WHO reference data. Subjects A total of 346 school-going native highlander children (4–19 years of age) were studied. Results Among the study population, the mean height was 141.17 ± 39.08 cm, the mean weight was 38.27 ± 25.40 kg. The gender difference in height, MUAC, sub-scapular skinfold (SSF) thickness, TSF thickness and the abdominal circumference was found to be statistically significant. Of the subjects 23.46% were stunted (i.e. HFA below −2 SD of the WHO standard) and 7.01% were underweight (WFA below −2 SD of the WHO standard). Conclusion The nutritional status of the Ladakhi population was assessed by comparison with the WHO reference data. Nomograms for anthropometric data in school-going children (4–19 years of age) of Ladakh were created. These can be used for further studies and planning targeted intervention strategies on this geographically isolated and evolutionary distinct highland population.