Tetrahydrobiopterin loading test in xanthine dehydrogenase and molybdenum cofactor deficiencies

The objectives of this study were to find additional diagnostic information for the evaluation of xanthine dehydrogenase deficiency and molybdenum cofactor deficiency. Patients were given an oral loading test with 10 mg/kg 5,6,7,8-tetrahydrobiopterin. Urine excretion of pterin and isoxanthopterin was measured by HPLC. Control subjects had a fairly constant ratio of urinary pterin/isoxanthopterin before (0.57-5.32) and after (0.55-4.55) 5,6,7,8-tetrahydrobiopterin loading. These ratios were increased to 33 and 22 in a patient with hereditary xanthinuria and to 570 and 8030 in a patient with molybdenum cofactor deficiency. Obligate heterozygotes had an entirely normal test result. Evidence was obtained for the in vivo involvement of xanthine dehydrogenase in the conversion of pterin to isoxanthopterin. This test could be a sensitive marker for the establishment of residual enzyme activity.