Whole-exome sequencing and variant spectrum in children with suspected inherited renal tubular disorder: the East India Tubulopathy Gene Study.

BACKGROUND: Inherited tubulopathies are a heterogeneous group of genetic disorders making whole-exome sequencing (WES) the preferred diagnostic methodology. METHODS: This was a multicenter descriptive study wherein children (< 18 years) with clinically suspected tubular disorders were recruited for molecular testing through WES. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were done when required. Variants were classified as per American College of Medical Genetics 2015 guidelines and pathogenic (P)/likely pathogenic (LP) variants were considered causative. RESULTS: There were 77 index cases (male =73%). Median age at diagnosis was 48 months (IQR 18.5 to 108 months). At recruitment, the number of children in each clinical group was as follows: distal renal tubular acidosis (dRTA) = 25; Bartter syndrome = 18; isolated hypophosphatemic rickets (HP) = 6; proximal tubular dysfunction (pTD) = 12; nephrogenic diabetes insipidus (NDI) = 6; kidney stone/nephrocalcinosis (NC) = 6; others = 4. We detected 55 (24 novel) P/LP variants, providing genetic diagnoses in 54 children (70%). The diagnostic yield of WES was highest for NDI (100%), followed by HP (83%; all X-linked HP), Bartter syndrome (78%), pTD (75%), dRTA (64%), and NC (33%). Molecular testing had a definite impact on clinical management in 24 (31%) children. This included revising clinical diagnosis among 14 children (26% of those with a confirmed genetic diagnosis and 18% of the overall cohort), detection of previously unrecognized co-morbidities among 8 children (sensorineural deafness n = 5, hemolytic anemia n = 2, and dental changes n = 1) and facilitating specific medical treatment for 7 children (primary hyperoxaluria n = 1, cystinosis n = 4, tyrosinemia n = 2). CONCLUSION: WES is a powerful tool in the diagnosis and management of children with inherited tubulopathies in the Indian population. A higher resolution version of the Graphical abstract is available as Supplementary information.

Cardiorenal syndrome in the pediatric population: A systematic review.

The concept of cardiorenal syndrome (CRS) is derived from the crosstalk between the heart and kidneys in pathological conditions. Despite the rising importance of CRS, there is a paucity of information on the understanding of its pathophysiology and management, increasing both morbidity and mortality for patients. This review summarizes the existing conceptual pathophysiology of different types of CRS and delves into the associated therapeutic modalities with a focus on pediatric cases. Prospective or retrospective observational studies, comparative studies, case reports, case-control, and cross-sectional studies that include pediatric patients with CRS were included in this review. Literature was searched using PubMed, EMBASE, and Google Scholar with keywords including "cardio-renal syndrome, type," "reno-cardio syndrome," "children," "acute kidney injury," and "acute decompensated heart failure" from January 2000 to January 2021. A total of 14 pediatric studies were ultimately included and analyzed, comprising a combined population of 3608 children of which 32% had CRS. Of the 14 studies, 57% were based on type 1 CRS, 14% on types 2 and 3 CRS, and 7% were on types 4 and 5 CRS. The majority of included studies were prospective cohort, although a wide spectrum was observed in terms of patient age, comorbidities, etiologies, and treatment strategies. Commonly observed comorbidities in CRS type 1 were hematologic, oncologic, cardiology-related side effects, muscular dystrophy, and pneumonia/bronchiolitis. CRS, particularly type 1, is prevalent in children and has a significant risk of mortality. The current treatment regimen primarily involves diuretics, extracorporeal fluid removal, and treatment of underlying etiologies and comorbidities.

Eastern India Collaboration on Multisystem Inflammatory Syndrome in Children (EICOMISC): A Multicenter Observational Study of 134 Cases.

Background: Few single center studies from resource-poor settings have reported about the epidemiology, clinical feature and outcome of multisystem inflammatory syndrome in children (MIS-C). However, larger data from multi-center studies on the same is lacking including from Indian setting. Methods: This retrospective collaborative study constituted of data collected on MIS-C from five tertiary care teaching hospitals from Eastern India. Children ≤ 15 years of age with MIS-C as per the WHO criteria were included. Primary outcome was mortality. Results: A total of 134 MIS-C cases were included (median age, 84 months; males constituted 66.7%). Fever was a universal finding. Rash was present in 40%, and conjunctivitis in 71% cases. Gastro-intestinal and respiratory symptoms were observed in 50.7% and 39.6% cases, respectively. Co-morbidity was present in 23.9% cases. Shock at admission was noted in 35%, and 27.38% required mechanical ventilation. Fifteen (11.2%) children died. The coronary abnormalities got normalized during follow-up in all except in one child. Initial choice of immunomodulation had no effect on the outcomes. Presence of underlying co-morbidity, lymphopenia, thrombocytosis, hyponatremia, increased LDH (>300 U/L), and hypoalbuminemia were the factors significantly associated an increased mortality. Conclusions: MIS-C has myriad of manifestations. Underlying co-morbidity, lymphopenia, thrombocytosis, hyponatremia, increased LDH (>300 U/L), and hypoalbuminemia were associated with an increased mortality. No difference in outcome was noted with either steroid or IVIg or both. Coronary artery abnormalities resolved in nearly all cases.