A rapid yet reliable chemical diagnosis for
dihydropyrimidine dehydrogenase (DHPD) deficiency, and possibly
dihydropyrimidinase (DHP) deficiency in
cancer patients, prior to
therapy with
pyrimidine analogues such as
5-fluorouracil, is desired for prevention of severe side-effects by these drugs. We have reported the basic separation and quantitation technology for
pyrimidine metabolites using gas chromatography-mass spectrometry. A proposal to use the number (n) of standard deviations (SD) above the normal mean, as the index of the excessive urinary excretion of the metabolites appears not to be commonly used. When used, the values were too small, such as two or three, even in
genetic disorders. Here, we applied the method to 11 urine specimens from proven cases including two DHP carriers and proved how specific the method is, because "n"-values were markedly large for
thymine (T),
uracil (U) and/or dihydrothymine (DHT) and
dihydrouracil (DHU). In three cases with DHPD deficiency, two were siblings, one with symptoms and the other without, n was 12 for T and 5.9 for U, and
5-hydroxymethyluracil was distinctly detected. These values indicate that the nature of genetic mutation relates closely to the degree of metabolite accumulation in
pyrimidine disorders. In six patients with DHP deficiency, n was 8.4-12 for DHT and 7.2-11 for DHU. Many mutations are known for both genes and the assay of residual
enzyme activity may be time-consuming or invasive especially for those with DHP deficiency. Thus, this noninvasive yet comprehensive urinalysis has great value for those without a family history, as the first trial, before
DNA or the
enzyme assay. Our findings again raise the question whether the metabolic block really causes the symptoms found in
pyrimidine disorders.