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.