Deficiency of Fumarylacetoacetase in the Acute Form of Hereditary Tyrosinemia with Reference to Prenatal Diagnosis

  • S. B. Melançon
  • R. Gagné
  • A. Grenier
  • A. Lescault
  • L. Dallaire
  • C. Laberge
  • M. Potier
Part of the Hepatology book series (H, volume 5)


The terms tyrosinemia and tyrosinosis have been widely used to describe at least seven distinct disorders of tyrosine metabolism associated with diverse clinical and biochemical consequences in infants, children and even adults (1). The only consistent biochemical abnormality within these syndromes has been the finding of elevated levels of plasma tyrosine, a non-essential amino acid derived from phenylalanine by the action of the enzyme phenylalanine hydroxylase. In most of the reported patients with tyrosinemia the clinical presentation resembled that of acute liver failure (acute infantile stage) while later manifestations (chronic stage) included liver cirrhosis, multiple renal tubular dysfunction, hypophosphatemic rickets and porphyria-like symptoms. Other less frequent modes of presentation were mental retardation, skin and corneal dystrophies and metabolic acidosis, without liver involvement. The major characteristics of the most common forms of tyrosinemia are outlined in Table I. For the purpose of this presentation, we will restrict our discussion to hereditary tyrosinemia.


Amniotic Fluid Corneal Dystrophy Homogentisic Acid Acute Intermittent Porphyria Tyrosine Metabolism 
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  1. 1.
    LA DUBN,GJESSINGLR: Tyrosinosis and Tyrosinemia. InThe Metabolic Basis of Inherited Disease, 4th Edition. JB Stanbury, JB Wyngaarden, DS Fredrickson (eds). McGraw Hill Co., N.Y. 1978. pp. 256–267.Google Scholar
  2. 2.
    WADMANSK,SPRANGFJ, VANMAASJW,KETTINGD: An exceptional case of tyrosinosis.J Ment Defic Res 12; 269–281, 1968.PubMedGoogle Scholar
  3. 3.
    LOUISWJ,PITTDD,DAVIESH: Biochemical studies in a patient with tyrosinosis.Aust NZ Jl Med 4:281–286, 1974.CrossRefGoogle Scholar
  4. 4.
    HARRIESJT,SEAKINSJWT,ERSSERRS,LLOYDJK: Recovery after dietary treatment of an infant with features of tyrosinosis.Arch Dis Child 44:258–267, 1969.PubMedCrossRefGoogle Scholar
  5. 5.
    JAISWALRB,BHAII,NATHN,NATHMC: Tyrosinosis, clinical, radiological and biochemical aspects.Indian Pediat 6: 1–17, 1969.Google Scholar
  6. 6.
    MEDESG: New error of tyrosine metabolism: tyrosinosis. Intermediary metabolism of tyrosine and phenylalanine.Biochem J 26: 917–940, 1932.PubMedGoogle Scholar
  7. 7.
    LABERGEC: Hereditary tyrosinemia in a French Canadian isolate.Am J Hum Genet 21: 36–45, 1969.PubMedGoogle Scholar
  8. 8.
    GENTZJ,JAGENBURGR,ZETTERSTROMR: Tyrosinemia: an inborn error of tyrosine metabolism with cirrhosis of the liver and multiple renal tubular defects.J Pediatr 66: 670–696, 1965.PubMedCrossRefGoogle Scholar
  9. 9.
    GAULLGE,RASSINDK,SOLOMONGE,HARRISRC,STURMANJA: Biochemical observations on so-called hereditary tyrosinemia.Pediatr Res 4: 337–344, 1970.PubMedCrossRefGoogle Scholar
  10. 10.
    WEINBERGAG,MIZECE,WORTHENHG: The occurrence of hepatoma in the chronic form of hereditary tyrosinemia.J Pediatr88: 434–438, 1976.PubMedCrossRefGoogle Scholar
  11. 11.
    GRENIERA,MORRISSETTEJ,DUSSAULT JH,LABERGEC,GAGNER: Les maladies métaboliques héréditaires au Québec: le dépistage sanguin.Union Med Can 109: 591–595, 1980.PubMedGoogle Scholar
  12. 12.
    GRENIERA,LABERGEC: A modified automated fluorometric method for tyrosine determination in blood spotted on paper: a mass screening procedure for tyrosinemia.Clin Chim Acta57: 71–75, 1974.PubMedCrossRefGoogle Scholar
  13. 13.
    GRENIERA,MORRISSETTEJ,VALETJP,BELANGERL:: Polystyrene tube immunoradiometric assay for human o¿i-fetoprotein, and its use for mass screening.Clin Chem 24: 2158–2160, 1978.PubMedGoogle Scholar
  14. 14.
    GAULLGE,RASSINDK,STURMANJA: Significance of hypermethioni-naemia in acute tyrosinosis.Lancet 1: 1318, 1966.Google Scholar
  15. 15.
    STRIFECF,ZUROWESTEEL,EMMETTEA,FINELLIVN,PETERINGHC,BERRYHK: Tyrosinemia with acute intermittent porphyria: aminolevulinic acid dehydratase deficiency related to elevated urinary aminolevulinic acid levels.J Pediatr90: 400–404, 1977.PubMedCrossRefGoogle Scholar
  16. 16.
    LINDBLADB,LINDSTEDTS,STEENG: On the enzymic defects in hereditary tyrosinemia.Proc Natl Acad Sci USA 74:4641–4645, 1977.PubMedCrossRefGoogle Scholar
  17. 17.
    HSIANGHH,SIMSS,MAHURANDJ,SCHMIDTDE: Purification and properties of a diketo acid hydrolase from beef liver.Biochemistry 11: 2098–2102, 1972.PubMedCrossRefGoogle Scholar
  18. 18.
    FISCHRO,MCCABEERB,DOEDEND,KOEPLJ,KOHLHOFFJG,SILVERMANA,STARZLTC: Homotransplantation of the liver in a patient with hepatoma and hereditary tyrosinemia.J Pediatr 93: 592–596, 1978.PubMedCrossRefGoogle Scholar
  19. 19.
    EBERTPS,HESSRA,FRYKHOLMBC,TSCHUDYDP: Succinylacetone, a potent inhibitor of heme biosynthesis: effect on cell growth, heme content and -aminolevulinic acid dehydratase activity of malignant murine erythroleukemia cells.Biochem Biophys Res Commun 88: 1382–1390, 1979.PubMedCrossRefGoogle Scholar
  20. 20.
    FERNSTROMJD,WURTMANRJ,HAMMARSTROM-WIKLUNDB,RANDWM,MUNROHN,DAVIDSONCS: Diurnal variations in plasma neutral amino acid concentrations among patients with cirrhosis: effect of dietary protein.Am J Clin Nutr 32:1923–1933, 1979.PubMedGoogle Scholar
  21. 21.
    PERRYTL,HARDWICKDF,HANSENS,POHLMANL,WARRINGTONPD: Methionine induction of experimental tyrosinaemia.J Ment Defic Res 11: 246–253, 1967.PubMedGoogle Scholar
  22. 22.
    MICHALSK,MATALONR,WONGPWK: Dietary treatment of tyrosinemia type I.J Am Diet Assoc 73: 507–514, 1978.PubMedGoogle Scholar
  23. 23.
    MONTGOMERYJA,MAMAEROA: Profiles in altered metabolism II: accumulation of homogentisic acid in serum and urine following acetylsalicylic acid ingestion.Biomed Mass Spectrom 5: 331–333, 1978.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • S. B. Melançon
    • 1
  • R. Gagné
    • 1
  • A. Grenier
    • 1
  • A. Lescault
    • 1
  • L. Dallaire
    • 1
  • C. Laberge
    • 1
  • M. Potier
    • 1
  1. 1.Quebec Network of Medical Genetics, Centre de Recherche Pédiatrique de l’Hôpital Sainte-JustineUniversité de Montréal and Centre Hospitalier de l’Université LavalCanada

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