In transfusion-dependent thalassemia, neuronal damage biomarkers are associated with affective and chronic fatigue symptoms

Patients with transfusion-dependent thalassemia (TDT) are vulnerable to neurotoxicity due to frequent blood transfusions and the subsequent iron overload (IO) and inflammation. This vulnerability may contribute to the development of depression, anxiety, and chronic fatigue syndrome (CFS). This case-control study aims to investigate central nervous system injury biomarkers, including neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), neurofilament light (NFL) and nestin, neuro-immune markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-10, calcium, magnesium, copper, zinc, hematocrit, hemoglobin, iron and ferritin in 126 children with TDT and 41 healthy children. We examined the associations between these biomarkers and the Fibro-Fatigue (FF) Rating Scale, the Children's Depression Inventory (CDI), and the Spence Children's Anxiety Scale (SCAS) scores. Children with TDT showed significantly elevated FF, CDI, and SCAS scores, IO (as assessed using iron and ferritin levels), and higher NSE, GFAP, NFL, CRP, IL-6 and IL-10, and lower magnesium, zinc, and calcium as compared with healthy children. There were significant correlations between the CDI score and NFL, NSE and GFAP, SCAS score and NFL, and FF score and NFL and GFAP. The neuronal damage biomarkers were significantly associated with biomarkers of IO (including iron and ferritin) and the erythron (including lowered hematocrit and hemoglobin). These results suggest that IO-associated neurotoxicity and inflammation in children with TDT may contribute to symptoms of depression, anxiety, and chronic fatigue and may serve as potential therapeutic targets.