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.


Chronic Form Acute Type Fanconi Syndrome Maple Syrup Urine Disease Tyrosine Aminotransferase 
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Succinyl acetone


Tyrosine aminotransferase


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© Springer-Verlag Berlin Heidelberg 1990

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  • S. Halvorsen

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