Metabolomic analysis of serum by (1) H NMR spectroscopy in amyotrophic lateral sclerosis

Abstract

Background: Amyotrophic lateral sclerosis (ALS), an invariably fatal neurological disorder shows complicated pathogenesis that poses challenges with respect to diagnosis as well as monitoring of disease progression. Methods: We investigated metabolite profiles in the serum of 30 patients with ALS, 10 patients of Hirayama disease, which served as a neurological disease control and 25 healthy controls by using (1) H NMR spectroscopy. Results: Compared to healthy controls, the ALS patients had higher quantities of glutamate (P < 0.001), beta-hydroxybutyrate (P < 0.001), acetate (P < 0.01), acetone (P < 0.05), and formate (P < 0.001), and lower concentrations of glutamine (P < 0.02), histidine (P < 0.001) and N-acetyl derivatives. On the other hand, Hirayama disease patients had significantly higher median concentrations of pyruvate (P < 0.05), glutamate (P < 0.001), formate (P < 0.05) and lower median concentrations of N-acetyl derivatives. Furthermore, we also found that serum glutamate showed a positive correlation (P < 0.001, r = 0.6487) whereas, histidine showed a negative correlation (P < 0.001, r = - 0.5641) with the duration of the disease in ALS. Conclusions: Such (1) H NMR study of serum may reveal abnormal metabolite patterns, which could have the potential to serve as surrogate markers for monitoring ALS disease progression.