Abstract
Type 1 hereditary tyrosinemia is an inborn error of tyrosine metabolism and presents itself shortly after birth as a severe liver and kidney disease. It is characterized by a profound deficiency of fumarylacetoacetase in liver, kidney and white blood cells. To investigate the nature of the enzym defect in more detail extracts of livers derived from patients were examined with immunochemical methods. Fumarylacetoacetase was purified (500x) from beef liver and antibodies against this protein were raised in rabbits. These antibodies cross react with the human liver enzyme. Analysis of liver extracts from type 1 hereditary tyrosinemia patients by immunodetection on blots showed the absence of cross reacting material in these livers. These findings could also be shown in extracts from extrahepatic tissues (kidney) and white blood cells (lymphocytes). Lack of cross reacting material could also be shown in cultured fibroblasts and amniotic fluid cells from patients. Thus the mutation causing type 1 hereditary tyrosinemia may lead to the synthesis of an aberrant enzym with a very short half-life, may affect the expression of the structural gene at the transcription/tranlational level or affects the proper expression of a regulatory gene. At present a human cDNA library is screened for probes in order to discriminate between these possibilities.
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Okken, A., Berger, R., Van Faassen, H. et al. 60 TYPE I HEREDITARY TYROSINEMIA: LACK OF IMMUNOLOGICALLY DETECTABLE FUMARYLACETOACETASE ENZYM PROTEIN IN TISSUES FROM PATIENTS. Pediatr Res 20, 1044 (1986). https://doi.org/10.1203/00006450-198610000-00114
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DOI: https://doi.org/10.1203/00006450-198610000-00114