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Background Enhanced availability of high-throughput sequencing (at progressively reducing costs) has revolutionized the identification of monogenic SRNS. However, in resource-poor settings, it may not be possible to perform next-generation sequencing (NGS) in all children wherein monogenic SRNS is suspected. Besides, the optimal strategy of genetic evaluation (in patients with SRNS) in routine clinical practice in resource-limited settings is unknown. Methods Patients with newly diagnosed SRNS were recruited from our center and followed up prospectively. We analyzed the factor(s) independently predicting the occurrence of disease-causing variants in these patients. Results In our study, 36 children/adolescents with SRNS were included (initial steroid resistance in 53%). On targeted NGS, pathogenic/likely pathogenic variants were identified in 31% (n = 11). These included homozygous or compound heterozygous variants in the following genes: ALOX12B, COL4A3, CRB2, NPHS1, NPHS2, PLCE1, and heterozygous variant in WT1 gene. Overall, 14 variants were identified of which 5 (36%) were novel. Age of < 1 or < 2 years and presence of family history of nephrotic syndrome independently predicted the occurrence of monogenic SRNS on multivariate analysis. Conclusions While NGS-based genetic testing in SRNS is increasingly being incorporated in routine clinical practice the world over, the scenario is far from optimal in resource-limited settings. Our study highlights that resources for genetic testing in SRNS should be prioritized for patients with early age at disease onset and presence of family history. Larger studies composed of diverse multi-ethnic cohorts of patients with SRNS are required to further delineate the optimal strategy of genetic evaluation in resource-poor settings. Graphical abstract, Author(s): Anit Kaur [sup.1] , Aaqib Zaffar Banday [sup.1] , Lesa Dawman [sup.2] , Amit Rawat [sup.1] , Karalanglin Tiewsoh [sup.2] Author Affiliations: (1) grid.415131.3, 0000 0004 1767 2903, Allergy [...]

Major histocompatibility complex class I deficiency results from deleterious biallelic variants in TAP1, TAP2, TAPBP, and B2M genes. Only a few patients with variant-curated TAP1 deficiency (TAP1D) have been reported in the literature and the clinical phenotype has been variable with an emphasis on autoimmune and inflammatory complications. We report TAP1D in a Nepalese girl with a severe clinical phenotype with serious viral infections at a very young age. A novel frameshift termination variant near the protein's amino (N-) terminal was found. Variants in exon 1 of the TAP1 gene (as in our case) have not been reported previously. We also perform a brief review of TAP1D that hints at potential genotype-phenotype correlations. However, these findings need to be interpreted with due prudence given the small number of patients with TAP1D reported thus far. [ABSTRACT FROM AUTHOR]

The article discusses a case of a young girl with a rare immune disorder called autoimmune lymphoproliferative syndrome (ALPS) due to a biallelic FASL gene mutation. The girl developed Hodgkin lymphoma and underwent a successful hematopoietic stem cell transplant as part of her treatment. The case highlights the challenges and successful management of ALPS-FASL and associated malignancies. The study emphasizes the importance of genetic analysis, regular monitoring, and appropriate treatment in such cases. [Extracted from the article]

Objectives Kawasaki disease (KD) is a medium vessel vasculitis with a predilection to involve coronary arteries. However, there is a paucity of literature on microvascular changes in patients with KD. Methods Children diagnosed with KD based on American Heart Association guidelines 2017 were enrolled prospectively. Demographic details and echocardiographic changes in coronaries were recorded. Nailfold capillaries were assessed using Optilia Video capillaroscopy and data were analysed using Optilia Optiflix Capillaroscopy software at acute (prior to IVIG administration) and subacute/convalescent phase. Results We enrolled 32 children with KD (17 boys) with a median age of 3 years. Nailfold capillaroscopy (NFC) was performed in 32 patients in the acute phase (compared with 32 controls) and in 17 during the subacute/convalescent phase at a median follow-up of 15 (15–90) days after IVIG treatment. The following findings were seen in NFC in the acute phase of KD: reduced capillary density (n  = 12, 38.6%), dilated capillaries (n  = 3, 9.3%), ramifications (n  = 3, 9.3%) and capillary haemorrhages (n  = 2, 6.2%). Capillary density was reduced significantly in the acute phase of KD (38.6%) as compared with the subacute/convalescent phase (25.4%) (P -value <0.001) and controls (0%) (P -value = 0.03). We observed no correlation between coronary artery involvement and mean capillary density (P  = 0.870). Conclusion Results show that patients with KD have significant nailfold capillary changes in the acute phase. These findings may provide a new diagnostic paradigm for KD and a window to predict coronary artery abnormalities. [ABSTRACT FROM AUTHOR]

The article in the Journal of Paediatrics & Child Health discusses the case of a 3-month-old infant with severe lactic acidosis and basal ganglia hyperintensities. The infant, who was exclusively breastfed, suffered from metabolic acidosis due to severe dietary restrictions imposed by her mother based on local social taboos. Treatment with intravenous vitamin Bx led to a rapid improvement in the infant's condition, and she is now doing well with normal development at 1 year of age. The likely diagnosis in this case is bilateral symmetrical hyperintensities in the basal ganglia and frontoparietal cortex on brain imaging. [Extracted from the article]