Exploring Dysregulated Plasma Metabolites in Sickle‐Cell Disease Patients Using Comparative NMR‐Based Metabolomics

Sickle-Cell Disease (SCD) is one of the most common autosomal recessive genetic blood disorders that manifest in abnormal behavior of the red blood cells (RBCs). The mutated Hb causes sickling of RBCs under deoxygenated conditions, reducing their flowing ability, pliability, and resulting in hemolysis. The pathophysiology observed in the Indian cohort varies regionally, with some Indian tribal populations depicting milder symptoms despite SCD being relatively prevalent among them. To understand the pathogenesis of SCD with respect to nongenetic parameters, we initiated a comparative untargeted metabolomics study of the eastern Indian cohort of SCD patients using ¹H NMR spectroscopy. In this exploratory study, we focused only on a small cohort of 26 SCD patients from the eastern part of India with relatively high prevalence of SCD. Our NMR-based metabolomics, in combination with statistical analyses, yielded 11 of the 29 identified metabolites that showed a statistically significant difference in concentrations between healthy controls and SCD patients. The dysregulated metabolites include molecules involved in glycolysis, hypoxic, and acute-stress conditions.