Disease Information for Tyrosinemia, hereditary: Definition

  • A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency; Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase; Type II tyrosinemia features mental retardation, painful corneal ulcers, and keratoses of the palms and plantar surfaces and is caused by a deficiency of the enzyme TYROSINE TRANSAMINASE; Type III tyrosinemia features mental retardation and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE (Menkes, Textbook of Child Neurology, 5th ed)----------------------------HEPATORENAL TYROSINEMIA (OR TYROSINEMIA TYPE I)

    Hepatorenal tyrosinemia (MIM 276700) is an autosomal recessive disorder in which the final enzyme in tyrosine catabolism, fumarylacetate hydrolase (FAH), is deficient; The fumarylacetoacetate that accumulates is converted nonenzymatically to succinylacetone, which is toxic to the liver and kidneys and which inhibits the porphyrin synthetic enzyme ALA dehydratase, causing sudden neurologic crises in some patients

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    Hereditary tyrosinemia is caused by deficiency of fumarylacetoacetase and is characterized by progressive hepatic parenchymal damage, renal tubular dystrophy with generalized amino acid urea and hypophosphatemic rickets, hypermethioninemia, and tyrosine metabolites, succinylacetone, and delta aminilevulinic acid in the urine; The course may be rapidly fatal in infancy was somewhat more chronic with liver cell carcinoma almost invariable; The condition is inherited as an autosomal recessive trait and is especially common in Scandinavia and St Jean region of Québec in Canada; Prenatal diagnosis can be established; Similar clinical and biochemical findings may occur in Galactosemia and Hereditary Fructose Intolerance but increased succinylacetone occurs only in fumarylacetoacetase deficiency and diagnosis is based on demonstrating this compound in the urine; Treatment: a diet low in phenylalanine and tyrosine is indicated but not usually successful in preventing or reversing liver damage and liver transplant appears to be the only effective therapy for these children; Experimental pharmacological therapy to inhibit 4-hydroxyphenylpyruvater dehydrogenase improves a biochemical profile and acute clinical status, and studies are in progress to determine to what extent this prevents hepatocellular carcinoma as well;

    ---------------[adapted Current Pediatrics Diagnosis and Treatment 14th ed 1999 Hay et al; Appleton Lange, Stamford, CT]-------------------