Elevated blood tyrosine levels are present in several
clinical entities. The term tyrosinemia is used to describe several
syndromes. In general, the association of liver and renal failure, marked peripheral
edema, epistaxis, and distinctive cabbage-like odor are characteristic of
the disease. There are three types of tyrosinemia-related syndromes.
Tyrosinemia type I: Hepatorenal Tyrosinemia;
Fumarylacetoacetase Deficiency; FAH Deficiency.
Tyrosinemia type II: Oculocutaneous Tyrosinemia; Tyrosine
Transaminase Deficiency; Tyrosine Aminotransferase Deficiency;
Richner-Hanhart Syndrome; Oregon type Tyrosinemia.
Tyrosinemia type III: 4-Hydroxyphenylpyruvic Acid Oxydase
Deficiency; 4-Hydroxyphenylpyruvate Dioxygenase Deficiency.
In the United States, the estimated incidence is
1:100,000 live births. However, most cases are seen in the French-Canadian
population of the Province of Quebec, with an incidence of carriers of a
specific mutation in 1:14 of the adult population and symptomatic
presentation in 1:1850 newborns.
Autosomal recessive in all cases. The sex
distribution is equal.
Deficiency of fumarylacetoacetate hydrolase
results in a moderate rise in serum tyrosine. Metabolites of tyrosine,
including succinylacetone, are thought to be the cause of liver, renal, and
neurological damage. Transient tyrosinemia is believed to be the result of
delayed enzyme maturation in the tyrosine catabolic pathway. Because it is
not caused by a genetic mutation, it does not fall into the category of
inborn errors of metabolism. In the hereditary infantile tyrosinemia (type
I) form, postmortem examination reveals the presence of severe liver and
kidney nodular cirrhosis.
Succinylacetone and succinylacetoacetate in blood and
urine are diagnostic. Enzyme deficiency demonstrable in liver biopsy
specimen or cultured fibroblasts.
Transient tyrosinemia of the newborn is benign and disappears spontaneously
with no sequelae.
Hereditary Infantile Tyrosinemia (type I) is a severe form of tyrosinemia. Patients present with peculiar
(cabbage-like) odor, renal tubular dysfunction (Fanconi Syndrome), and have
a survival rate of fewer than 12 months of life. Fulminant onset of liver
failure occurs in the first few months of life. Occasional cases have a
later onset; however, the patient is usually younger than age 6 months. This
acute form presents with failure to thrive and severe vomiting. Progressive
hepatic failure results in death before 2 years of age.
Richner-Hanhart Syndrome (Tyrosinemia type II) is distinctly different with herpetiform corneal ulcers and hyperkeratotic
lesions of the tongue, digits, palms, and soles, as well as mental
retardation. Most patients are photophobic in bright light. In this more
chronic from, deterioration may not occur after first year of life. Patients
fail to thrive and develop liver cirrhosis, renal tubular dysfunction, and
vitamin D-resistant rickets. Episodes of polyneuropathy, which often cause
severe pain, occur in some patients. Death occurs by age 10 years from
hepatic failure or hepatoma. Patients are typically chronically anemic and
have a coagulopathy secondary to liver failure. They are most often on
protein-restricted diet or phenylalanine-restricted diet.
Tyrosinemia type III is an extremely rare cause of ...