title: Hereditary tyrosinemia type I: lack of correlation between clinical findings and amount of immunoreactive fumarylacetoacetase protein.
abstract: Immunoblot analyses with bovine fumarylacetoacetase antibodies have been performed in fibroblast extracts from 28 patients with hereditary tyrosinemia of various clinical phenotypes, in one healthy individual homozygous for a "pseudodeficiency" gene for fumarylacetoacetase, and in three tyrosinemia families in which one or both parents are compound heterozygotes for the tyrosinemia and pseudodeficiency genes. Liver extracts from two chronic patients were also investigated. None of the patients with the acute type of tyrosinemia had detectable immunoreactive protein in fibroblast extracts. Only two of seven patients with typical chronic tyrosinemia had definite immunoreactivity in fibroblasts. In liver tissue, one of the patients had cross-reactive material and the other had no immunoreactivity. Four of 13 patients with intermediate clinical findings showed immunoreactivity in fibroblasts. There was no relationship between severity of symptoms and amount of cross-reactive material in this group. The pseudodeficiency gene product gave almost no detectable immunoreactivity in fibroblasts. The results indicate that chronic tyrosinemia may be due to at least two protein variants, and immunoblotting does not classify tyrosinemia patients according to clinical findings.
authors.affiliation: Institute of Clinical Biochemistry, Rikshospitalet, Oslo, Norway.
authors.forename: E A
authors.initials: EA
authors.lastname: Kvittingen
authors.forename: H
authors.initials: H
authors.lastname: Rootwelt
authors.forename: T
authors.initials: T
authors.lastname: van Dam
authors.forename: H
authors.initials: H
authors.lastname: van Faassen
authors.forename: R
authors.initials: R
authors.lastname: Berger
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000145:classification / Q000201:enzymology* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006867:Hydrolases / Q000032:analysis / Q000172:deficiency* / Q000235:genetics; D007120:Immunochemistry; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology; D008297:Male; D010375:Pedigree; D014443:Tyrosine / Q000097:blood*
chemical_list: D014443:Tyrosine; D006867:Hydrolases; C020156:fumarylacetoacetase