An association study of severity of intellectual disability with peripheral biomarkers of disabled children in a rehabilitation home, Kolkata, India

Abstract

The current investigation has identified the biomarkers associated with severity of disability and correlation among plethora of systemic, cellular and molecular parameters of intellectual disability (ID) in a rehabilitation home. The background of study lies with the recent clinical evidences which identified complications in ID. Various indicators from blood and peripheral system serve as potential surrogates for disability related changes in brain functions. ID subjects (Male, age 10 ± 5 yrs, N = 45) were classified as mild, moderate and severe according to the severity of disability using standard psychometric analysis. Clinical parameters including stress biomarkers, neurotransmitters, RBC morphology, expressions of inflammatory proteins and neurotrophic factor were estimated from PBMC, RBC and serum. The lipid peroxidation of PBMC and RBC membranes, levels of serum glutamate, serotonin, homocysteine, ROS, lactate and LDH-A expression increased significantly with severity of ID whereas changes in RBC membrane β-actin, serum BDNF, TNF-α and IL-6 was found non-significant. Structural abnormalities of RBC were more in severely disabled children compared to mildly affected ones. The oxidative stress remained a crucial factor with severity of disability. This is confirmed not only by RBC alterations but also with other cellular dysregulations. The present article extends unique insights of how severity of disability is correlated with various clinical, cellular and molecular markers of blood. This unique study primarily focuses on the strong predictors of severity of disability and their associations via brain-blood axis.

Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome

“…Finally, biomarker development is one of the biggest challenges for identifying underpinning causes of developmental disorders, which is crucial for effective therapeutic intervention ( Symons & Roberts, 2013 ; Anderson, 2015 ; Zafarullah & Tassone, 2019 ). For this, a variety of potential biomarkers for intellectual disability disorders have been proposed including monitoring of heart activity ( Tonnsen et al, 2013 ), blood cell signatures ( Sengupta et al, 2019 ), metabolic ( Berry-Kravis et al, 2015 ), inflammatory ( Manti et al, 2018 ), and signalling molecules ( Weng et al, 2008 ). Here, we show that the photoABP approach is a robust assay to monitor dysregulated RNF12 E3 activity in patients caused by TOKAS gene variants.…”

A Case of Potential Inborn Error of Metabolism as a Cause of Young Onset Psychosis

“…There is also increasingly robust evidence suggesting lactate related abnormalities may underpin cognitive dysfunction as well [12]. Recent evidence from domiciliary settings also suggest extant relationships between lactate levels and intellectual disability [13].…”

“…A general diagnostic strategy is suggested in these cases [13,14]. IEMs are usually suspected where there is a family history; if there are clinical signs triggered by conditions involving increased protein catabolism, e.g.…”

<p>Reduced Intellectual Ability in Offspring Born from Preeclamptic Mothers: A Prospective Cohort Study</p>

“…35 In addition, elevated Hcy levels appear to impair endothelium and lead to ischemic hypoxia through impaired nitric oxide-dependent vasodilation, endothelial toxicity and injury, oxidative stress, and systemic inflammation. [36][37][38][39][40] A recent study reported a significant association of serum Hcy concentration with the severity of the intellectual disability, 41 and increased plasma Hcy levels have also been identified as an independent risk factor for cognitive decline and atrophic changes in the brain. [42][43][44] It is therefore hypothesized that mothers with preeclampsia may present endothelial dysfunction induced by elevated Hcy levels, which results in hypoxic damages and leads to subsequent adverse effects on fetal neurodevelopment.…”