Central Tetrahydrobiopterin Concentration in Neurodevelopmental Disorders

Tetrahydrobiopterin (BH(4)) is a naturally occurring cofactor essential for critical metabolic pathways. Studies suggest that BH(4) supplementation may ameliorate autism symptoms; the biological mechanism for such an effect is unknown. To help understand the relation between central BH(4) concentration and systemic metabolism and to develop a biomarker of central BH(4) concentration, the relationship between cerebrospinal fluid BH(4) concentration and serum amino acids was studied. BH(4) concentration was found to be distributed in two groups, a lower and higher BH(4) concentration group. Two serum amino acids, citrulline and methionine, differentiated these groups, and the ratio of serum citrulline-to-methionine was found to correlate with the cerebrospinal fluid BH(4) concentration (r = −0.67, p < 0.05). Both citrulline and methionine are substrates in inflammation and oxidative stress pathways – two pathways that utilize BH(4) and are abnormally activated in autism. These data suggests that central BH(4) concentration may be related to systemic inflammation and oxidative stress pathways.