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

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 AILS disease progression. (C) 2010 Elsevier B.V. All rights reserved.