Summary
The enzymatic defect in hereditary tyrosinemia type I is reduced activity of fumarylacetoacetase. Determination of succinyl acetone (SA) in the urine and of fumarylacetoacetase activity in lymphocytes or fibroblasts confirms the diagnosis. Clinical heterogeneity is characteristic of this disorder. The symptoms may start during the first few months (acute type), in the second half of the first year (subacute type), or in the following years up to the teens (chronic types). In the acute type symptoms and signs of hepatic failure predominate. Vomiting, diarrhea, edema, ascites, bleeding tendency, and rapid deterioration is typical. In the subacute type the same symptoms may develop, but usually not to the same extent. Hepatomegaly and/or rickets may be presenting findings. In the chronic forms two main types may be distinguished; one with and one without tubulopathy and rickets. The former type is the most common. A rare subgroup has porphyrialike symptoms with hypertension, abdominal pains, muscular weakness, and hyperparesthesia. Glomerular filtration failure is another rare complication. The patients without tubulopathy and rickets present with hepatomegaly, failure to thrive, or thrombocytopenia. Hepatoma may develop in all types of hereditary tyrosinemia. Mental retardation is not a symptom of hereditary tyrosinemia. Dietary treatment may be lifesaving in acute cases. It improves the general condition in the chronic forms, improves tubular dysfunction and growth, and may postpone development of hepatoma. Liver transplantation is the only curative treatment, but difficulty remains in deciding the optimal time for transplantation. Ideally it should be performed before hepatoma develops. The inheritance is autosomal recessive.
Tyrosinemia type II is caused by deficiency of the liver-specific cytosolic enzyme tyrosine aminotransferase. The main symptoms are keratitis and clouding of the cornea, palmar and plantar erosions and hyperkeratosis, and in about half the patients mental retardation. There are markedly elevated serum tyrosine levels, overflow tyrosinuria, and tyrosyluria. Dietary treatment with phenylalanine and tyrosine restriction rapidly heals the eye and skin symptoms. The inheritance is autosomal recessive and the tyrosine aminotransferase gene locus has been assigned to chromosome 16q22.1→q23.3.
Transitory tyrosinemia of the newborn has an exogenous cause. The incidence of elevated serum tyrosine levels in the newborn infant depends on protein intake. Lethargy has been reported, otherwise no definite side effects are observed. The basis for the high serum tyrosine levels is delayed maturation of parahydroxyphenylpyruvate dioxygenase.
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Abbreviations
- SA:
-
Succinyl acetone
- TAT:
-
Tyrosine aminotransferase
References
Lindblad B, Lindstedt S, Steen G (1977) On the enzymic defects in hereditary tyrosinemia. Proc Natl Acad Sci USA 74: 4641–4645
Kvittingen EA, Halvorsen S, Jellum E (1983) Deficient fumarylacetoacetate fumarylhydrolase activity in lymphocytes and fibroblasts from patients with hereditary tyrosinemia. Pediatr Res 14: 541–544
Halvorsen S, Pande H, Christie Loken AA, Gjessing LR (1966) Tyrosinosis. A study of 6 cases. Arch Dis Child 41: 238–249
Halvorsen G, Gjessing LR (1964) Studies on tyrosinosis: 1. Effect of low-tyrosine and lowphenylalanine diet. Br Med J 2: 1171–1173
Larochelle J, Mortezai A, Belanger M, Tremblay M, Claveau JC, Aubin G (1964) Experience with 37 infants with tyrosinemia. Can Med Assoc J 97: 1051–1054
Sovik O, Kvittingen EA, Steen Johnsen J, Halvorsen S (1988) Hereditary tyrosinemia with unusual phenotypic expression. Pediatr Res 24: 266
Gentz J, Johansson S, Lindblad B. Lindstedt S, Zetterstrom R (1969) Excretion of 6-aminolevulinic acid in hereditary tyrosinemia. Clin Chim Acta 23: 257–262
Pettit BR, MacKnezie F, King GS, Leonard JV (1984) The antenatal diagnosis and aid to the management of hereditary tyrosinaemia by use of a specific and sensitive GC-MS assay for succinylacetone. J Inherited Metab Dis [Suppl] 2: 135–136
Grenier A, Lecault A, Laberge C, Gagne R, Mamer 0 (1982) Detection of succinylacetone and the use of its measurement in mass screening for hereditary tyrosinemia. Clin Chim Acta 123: 93–99
Kvittingen EA (1986) Hereditary tyrosinemia type I–an overview. Scand J Clin Lab Invest 46 [Suppl 1841: 27–34
Kvittingen EA, Brodtkorb (1986) The pre-and post-natal diagnosis of tyrosinemia type I and the detection of the carrier state by assay of fumarylacetoacetase. Scand J Clin Lab Invest 46 [Suppl 184]: 35–40
Halvorsen S, Kvittingen EA, Flatmark A (1988) Outcome of therapy of hereditary tyrosinemia. Acta Paediatr Jpn 30: 425–428
Bickel H, Schmidt H (1980) Clinical aspects of the treatment of Phenylketonuria (PKU). In: Bickel H, Hudson FP, Woolf L (eds) Phenylketonuria and some other inborn errors of amino acid metabolism. Thieme, Stuttgart, p 232
Kappas A, Sassa S, Galbraith RA, Nordmann Y (1989) The porphyrias. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1305–1365
Holme E, Lindblad B, Lindstedt S (1985) Possibilities for treatment and for early prenatal diagnosis of hereditary tyrosinaemia. Lancet I: 527
Starzl TE, Zitelli BF, Shaw BW, Iwatsuki S, Gartner JC, Gordon RD, Malatack JJ, Fox IJ, Urbach AH, van der Thiel DH (1985) Changing concepts: liver replacement for hereditary tyrosinemia and hepatoma. J Pediatr 106: 604–606
Kvittingen EA, Borresen AL, Stokke O, van der Hagen, Lie SO (1985) Deficiency of fumarylacetoacetase without hereditary tyrosinemia. Clin Genet 27: 550–554
Berger R, van Faassen H, van der Bergh I, Agsteribbe E, Wiemer E (1988) Different types of mutations in chronic and acute forms of type I tyrosinemia. Pediatr Res 24: 266
Schweizer W (1947) Studies on the effect of I-tyrosine on the white rat. J Physiol 106: 167–174
Goldsmith LA, Laberge C (1989) Tyrosinemia and related disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 547–562
Salamon T, Hrnjica M, Schnyder UW, Lazovié O, Softié M, Topié B, Stolié V, Popovié N, Cerkez A, Basié V (1988) Vier Fälle von Richner-Hanhart-Syndrom ( Tyrosinämie Typ II) mit neurologischer Symptomatologie in einer jugoslawischen Familie. Hautarzt 39: 149–154
Natt E, Westphal EM, Toth-Fejel SV, Magenis RE, Buist NRM, Rettenmeier R, Scherer G (1987) inherited and de novo deletion of the tyrosine aminotransferase gene locus at 16g22.1—.822.3 in a patient with tyrosinemia type II_ Hum Genet 77: 352–358
Sandberg HO (1975) Bilateral keratopathy and tyrosinosis. Acta Ophtalmol 53: 760–764
Halvorson S (1980) Screening for disorders of tyrosine metabolism. In: Bickel H, Guthrie R, Hammersen G (eds) Neonatal screening for inborn errors of metabolism. Springer, Berlin Heidelberg New York
Kindt E, Halvorsen S (1980) The need of essential amino acids in children. An evaluation based on the intake of phenylalanine, tyrosine, leucine, isoleucine and valine in children with phenylketonuria, tyrosine aminotransferase defect, and maple syrup urine disease. Am J Clin Nutr 33: 279–286
Fellman JH, Vanbellinghen PJ, Jones RT, Koler RD (1969) Soluble and mitochondrial forms of tyrosine aminotransferase. Relationship to human tyrosinemia. Biochemistry 8: 615–622
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© 1990 Springer-Verlag Berlin Heidelberg
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Halvorsen, S. (1990). Tyrosinemia. In: Fernandes, J., Saudubray, JM., Tada, K. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-02613-7_16
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