Abstract
Metabolism of thymine (T) and uracil (U) was investigated in 6 healthy volunteers (HV), and in a girl CW with dihydropyrimidine dehydrogenase (DHPD) deficiency and her mother JW and halfbrother HW. Three HV were loaded with T, the other three with U. CW, JW and HW were loaded with both. Dosis: 1 mmol/kg b.w. orally.
Plasma T on loading did not exeed 1.0 mM in the HV, but in CW and JW much higher values were found. In HW the concentrations were slightly above the highest values seen in the HV. The levels of 5-OH methyl-uracil (5-HMU) 2 hrs after loading ranged from 4-12 μM in the HV, from 21–34 μM in CW, JW and HW. Only in the HV and in HW significant and increasing amounts of nlasma β-aminoisobutyric acid(β-AIB) were seen. Plasma U reached max. values from 0.87-1.0 MM. β-Alanine (β-Ala) was undectable in all plasma samples.
After loading the excretion (mmol/great/12hr) of T in HV, JW and HW was in the same range (5.2-17), but in CW it was much higher (40.2). 5-HMU was excreted in all cases (0.6-2.9); in CW 2.5 mmol/g creat/12hr). On loading the excretion (mmol/g creat/12hr) of β-AIB was very high in the HV (18.9–21.3), intermediate in JW and HW (8.7 resp. 7.2) and low in CW (0.7). On loading with U, the excretion (mmol/g creat/12hr) of U was below 34.0 in the HV, JW and HW, but in CW it was 84.5. β-Ala was low in all urine samples (≤0.08). These results show that T or U loading can be used for the diagnosis of DHPD-deficiency. Loading with T seems to be more discriminative than U in detecting heterozygotes. Moreover, β-AIB gave valuable additional information about the (residual) capacity of T-catabolism. 5-HMU and β-Ala provided no diagnostic information.
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Van Gennip, A., Elzinga-Zoetekouw, L., Scholten, L. et al. 41 COMPARATIVE STUDY OF THYMINE AND URACIL METABOLISM IN HEALTHY PERSONS AND IN A PATIENT WITH DIHYDROPYRIMIDINE DEHYDROGENASE DEFICIENCY. Pediatr Res 24, 118 (1988). https://doi.org/10.1203/00006450-198807000-00065
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DOI: https://doi.org/10.1203/00006450-198807000-00065