Normal values and age-dependent changes in GTP cyclohydrolase I activity in stimulated mononuclear blood cells measured by high-performance liquid chromatography

GTP cyclohydrolase I (GCH1) activity in phytohemaglutinin (PHA)-stimulated mononuclear blood cells (MBCs) is a useful clinical marker for diagnosis of tetrahydrobiopterin (BH4)-related genetic disorders such as recessively inherited GCH1 deficiency and dominantly inherited dopa-responsive dystonia (Segawa’s disease). Since the assay is complex, including isolation of MBCs from blood, stimulation of MBCs by PHA under culture, isolation of the protein fraction from the PHA-stimulated MBCs, and the subsequent activity measurement, the reproducibility is problematic in its application to clinical study. We established a sensitive and reproducible method by high-performance liquid chromatography with fluorescence detection for clinical assay of GCH1 in PHA-stimulated MBCs, and measured the normal values of 91 healthy males and females of various ages (1–74 years). The mean normal values were 19.1±0.9 pmol/mg protein per h (mean±S.E., n=91). There were no significant differences between males and females. The activity tends to be higher in the first decade and to be decreased from the second to third decade and becomes almost stable from the third decade.