Oral loading of homogentisic acid in controls and in obligate heterozygotes for hereditary tyrosinemia type I.

Homogentisic acid (HGA) (50 mg/kg) was given orally to 22 obligate heterozygotes for hereditary tyrosinemia type 1 (HT) and to 11 controls. After 1 h the mean +/- standard error (SE) plasma level of HGA was 30.42 +/- 1.41 micrograms/ml in carriers and 19.29 +/- 1.62 in controls. Mean +/- SE fasting delta-amino-levulinate dehydratase (delta-ALD) was 40.05 +/- 1.79 m microM/min/g Hb in carriers, much lower than the 60.81 +/- 5.11 found in controls. After 3 h this difference in levels of delta-ALD remained, with mean +/- SE values of 25.70 +/- 2.89 m microM/min/g Hb in carriers, compared with 48.83 +/- 5.37 in controls. Three-hour mean +/- SE excretion of fumarylacetone "equivalent" [FAc] in urine in carriers, 51.597 +/- 5.580 micrograms/mg/creatinine, was significantly higher than the 27.941 +/- 5.916 in controls. Three-hour excretion of succinylacetone "equivalent" [SAc] was also significantly higher in the urine of carriers. FAc in 3-h urine was identified by thin-layer chromatography and confirmed by gas chromatography/mass spectrometry. Multivariate stepwise discriminant analysis showed that the inclusion order of significant variables was as follows: HGA levels at 1 hr, fasting level of delta-ALD, residual level of HGA at 3 h, and 3-h excretion of [FAc]. Non-significant variables were HGA tolerance, levels of delta-ALD at 3 h, sex, and 3-h excretion of [SAc].(ABSTRACT TRUNCATED AT 250 WORDS)