Metabolomics in sickle cell disease: Current knowledge and gaps – A scoping review

Abstract

Hemoglobinopathy; Mass spectrometry; Metabolism

Hemoglobinopatía; Espectrometría de masas; Metabolismo

Hemoglobinopatia; Espectrometria de masses; Metabolisme

Sickle cell disease (SCD) has large phenotypic variability. Systematic metabolomic profiling may provide insights into phenotypes and treatment responses. We conducted a scoping review on associations between blood metabolites, SCD-related complications, and therapies in studies analyzing ≥10 metabolites in red blood cells, whole blood, and plasma. Lipidomics-focused studies were excluded. Fifteen studies were included, focusing on metabolic profiling, clinical outcomes, or therapies (hydroxyurea, transfusion, and mitapivat). Metabolic profiling differentiated SCD from healthy controls and patients with HbSS and HbSC genotypes. Associations with hemolysis, vaso-occlusive events, nephropathy, TRV, and mortality were identified. Overall, metabolites were involved in arginine, tryptophan, glutamate metabolism, glycolysis, pentose phosphate pathway, and the Lands cycle. Some metabolites showed opposite correlations across complications or sample types. Despite growing interest, gaps remain in study designs, metabolite selection, genotype representation, and underexplored complications and therapies. Standardized, large-scale metabolomics studies are needed to advance personalized treatment in SCD.

This scoping review was supported by: • GA 101017549 – GENOMED4ALL - H2020-SC1-FA-DTS-2020-1. ‘Genomics and Personalized Medicine for all through Artificial Intelligence in Haematological Diseases’. • GA 101085717 – ERN-EuroBloodNet – EU4H-2022-ERN-IBA-01 - European Reference Network on Rare hematological diseases – ERN-EuroBloodNet.