Tyrosinemia

Tyrosinemia is a disease characterized by the deficiency of the enzymes tyrosamine transferase, 4-hydroxyphenyl pyruvate dioxygenase or fumarylacetoacetate hydrolase in the body.

But only in tyrosamine transferase deficiency, which means tyrosinemia type II, the clinical picture of the disease is due to high levels of tyrosine.

The role of excess tyrosine in the pathogenesis of the disease, provided that there is a deficiency of the other two enzymes, remains unknown for now.

Insufficient amount of the other two enzymes carrying out the exchange of tyrosine affects only to a small extent its levels in the blood plasma.

The acquired form of the disease is most often found in scurvy, because vitamin C is a coenzyme of 4-hydroxyphenyl pyruvate dioxygenase, severe liver disease, and in thyrotoxicosis in humans.

The first type of the disease is hereditary in humans and refers to autosomal recessive clinical conditions.

The fumarylacetoacetate hydrolase gene, which is associated with the development of the disease, has about 30 mutations.

There are three types of tyrosemia. The first type is most common among Scandinavians and the population of the French-speaking part of Canada.

Prenatal diagnosis is also offered by taking samples of the amniotic fluid and using them to test the enzyme activity in the placenta. In some cases, direct genetic analysis is done.

What are the symptoms?

Type I

The symptoms of this form of the disease primarily affect the kidneys, liver and peripheral nerves.

It begins with a liver crisis in intercurrent diseases, in which the body has difficulty breaking down proteins. The body temperature in most cases is elevated.

Among the most pronounced clinical manifestations are:

• Irritability;
• Vomiting, sometimes the vomited contents are bloody;
• Hematuria;
• Melena;
• Hepatomegaly;
• Hypoglycemia;
• Increase in the activity of serum transaminases;

The baby may smell like boiled cabbage due to the accumulation of methionine metabolites in his body.

The crises characteristic of the disease often resolve spontaneously, and in some cases liver failure develops, ending fatally.

Between the crises developmental arrest, prolonged disorders in the blood clotting process and hepatomegaly are often observed.

At the age of 2, the child developed liver cancer and cirrhosis. Malignant formation of the liver occurs in 37 out of every 100 sufferers

And in almost 40% of the sick children, attacks of peripheral neuropathy, similar to those in acute porphyria, were observed.

They can be triggered by mild infections and are characterized by increased muscle tone, severe muscle pain, twisting of the neck and body due to the hypertonicity, paralytic ileus and vomiting.

The condition described above creates conditions for the child to self-harm. 30% of attacks develop temporary muscle paralysis and severe muscle weakness.

Type II

This form of the disease is also classified as autosomal recessive. It manifests itself as erosion of the cornea, resembling herpes, areas of hyperkeratosis are formed on the skin of the hands and feet, retardation in mental development is also observed.

Type III

The disease begins at the age of 1-17 months, is mainly manifested by developmental delay, ataxic attacks, seizures and unusual behavior. In clinical practice, they are fixed on the liver and kidneys.

Treatment of tyrosinemia

In some cases, a diet without tyrosine and phenylalanine is effective. But in most cases the disease continues to develop.

Inhibitors of 4-hydroxyphenyl pyruvate dioxygenase, which are administered in parallel with the diet, are effective. No liver or neurological crises were observed in the patients who received treatment.

But it is still too early to say whether this combination therapy can prevent liver cancer.