Neopterin and Tetrahydrobiopterin Cerebrospinal Fluid Elevations in Aicardi Goutieres Syndrome: Confirmation of Findings in Mutation Confirmed Subjects (P05.134)

Abstract

Objective: We sought to validate previous findings of cerebrospinal fluid (CSF) Neopterin and Tetrahydrobiopterin abnormalities in mutation confirmed subjects with Aicardi Goutieres Syndrome. Background Previous reports of elevated Neopterin and Tetrahydrobiopterin in AGS predate molecular diagnosis in this disorder. Thus, their value as biomarkers remains difficult to ascertain. In addition, abnormal levels of 5-methyltetrahydrofolate have been reported in a few patients but the prevalence of this finding is unknown. Design/Methods: Twenty patients with mutation confirmed AGS, evaluated either at the International Aicardi Goutieres Syndrome Association or in the Myelin Disorders Bioregistry Project were studied retrospectively according to IRB approved protocols. CSF analysis was performed according to standard diagnostic approaches in AGS. Levels of alpha interferon (IFNa), Neopterin, Biopterin or Tetrahydrobiopterin and 5-methyltetrahydrofolate (5MTHF) were recorded. Results: Neopterin elevations (from 1.5 to 60.4 times the upper limit of normal for the analyzing laboratory) were identified in 16/20 subjects (709 + 587 nmol/l). Concomitant biopterin (102 + 62 nmol/l in 8/9 patients, from 1.5 to 6.9 the upper limit of normal) or tetrahydrobiopterin (120 + 47 nmol/l in 4/5 patients, from 1.1 to 3.1 the upper limit of normal) elevations were identified in 12/16 subjects, with no measurement in two subjects. In 11/16 subjects with elevated neopterin, IFNa was measured and found to be elevated in all but one. 5MTHF was measured in 14/20 subjects, and values were elevated in two (79.4 nmol/l and 144 nmol/l), low in five (34 + 17 nmol/l) and normal in the other seven. In all but one subject, low 5MTHF levels were associated with elevations in Neopterin and Biopterin or Tetrahydrobiopterin. Conclusions: Elevations of Neopterin and Biopterin or Tetrahydrobiopterin are present in a majority of subjects with mutation proven AGS. Levels of 5MTHF are variable and not as helpful as a diagnostic tool. Disclosure: Dr. Tonduti has nothing to disclose. Dr. Vanderver has nothing to disclose. Dr. Olivieri has nothing to disclose. Dr. Loewenstein has nothing to disclose. Dr. Fazzi has nothing to disclose. Dr. La Piana has nothing to disclose. Dr. Orcesi has nothing to disclose.