Metabolomics of cerebrospinal fluid reveals candidate diagnostic biomarkers to distinguish between spinal muscular atrophy type II and type III

Abstract

AimsClassification of spinal muscular atrophy (SMA) is associated with the clinical prognosis; however, objective classification markers are scarce. This study aimed to identify metabolic markers in the cerebrospinal fluid (CSF) of children with SMA types II and III.MethodsCSF samples were collected from 40 patients with SMA (27 with type II and 13 with type III) and analyzed for metabolites.ResultsWe identified 135 metabolites associated with SMA types II and III. These were associated with lysine degradation and arginine, proline, and tyrosine metabolism. We identified seven metabolites associated with the Hammersmith Functional Motor Scale: 4‐chlorophenylacetic acid, adb‐chminaca,(+/−)‐, dodecyl benzenesulfonic acid, norethindrone acetate, 4‐(undecan‐5‐yl) benzene‐1‐sulfonic acid, dihydromaleimide beta‐d‐glucoside, and cinobufagin. Potential typing biomarkers, N‐cyclohexylformamide, cinobufagin, cotinine glucuronide, N‐myristoyl arginine, 4‐chlorophenylacetic acid, geranic acid, 4‐(undecan‐5‐yl) benzene, and 7,8‐diamino pelargonate, showed good predictive performance. Among these, N‐myristoyl arginine was unaffected by the gene phenotype.ConclusionThis study identified metabolic markers are promising candidate prognostic factors for SMA. We also identified the metabolic pathways associated with the severity of SMA. These assessments can help predict the outcomes of screening SMA classification biomarkers.