fumarates and succinylacetone

A patient is described with type I tyrosinemia characterized by urinary excretion of succinylacetone together with increased excretion of tyrosine, p-hydroxyphenyllactic, p-hydroxyphenylpyruvic and p-hydroxyphenylacetic acids. Fumarylacetoacetase was measured in a liver biopsy and found to be very low compared to control liver. Furthermore the mass spectra of succinylacetone and fumarylacetoacetate (methoxime-TMS derivatives) are reported. Control jejunal mucosa, leucocytes and fibroblasts showed no enzyme activity; hence the prenatal diagnosis of this disease by measuring the fumarylacetoacetase activity in cultured amniotic fluid cells is not possible at present.

Topics: Acetoacetates; Amino Acid Metabolism, Inborn Errors; Fumarates; Heptanoates; Humans; Hydrolases; Infant; Keto Acids; Liver; Male; Tyrosine

Succinylacetone was excreted in the urine from four patients, with hereditary tyrosinemia i.e., two patients with the severe infantile type with fatal outcome and two patients with less severe juvenile form. In the urine from two patients with neonatal transient tyrosinemia and from normal individuals succinylacetone was not detectable. The urinary excretion of delta-aminolevulinic acid was also increased in all patients with hereditary tyrosinemia compared to patients with neonatal transient tyrosinemia and to normal individuals. The results presented support the hypothesis of a deficiency of fumarylacetoacetase in hereditary tyrosinemia. Furthermore an analytical method for the quantitative determination of succinylacetone in urine using GC-MS is described.

Topics: Acetoacetates; Amino Acid Metabolism, Inborn Errors; Aminolevulinic Acid; Female; Fumarates; Heptanoates; Heptanoic Acids; Humans; Hydrolases; Infant; Keto Acids; Levulinic Acids; Male; Models, Biological; Tyrosine