Tyrosinemia

As tyrosinemia are a group of rare, autosomal recessive, genetic metabolic diseases in which the metabolism of the amino acid tyrosine is disturbed. You have an increased level jointly by tyrosine in the blood. There are three types of the disease, which differ in severity and prognosis depending on the underlying enzyme defect.

Tyrosinemia type I

• See also: Main article tyrosinemia type I

This shape is also referred to as tyrosinemia hepatorenal because it damages both liver, kidney and brain in the full-blown disease. The disease is a mutation based on chromosome 15. The mutation makes for a deficiency of the enzyme Fumarylacetoacetase, which catalyzes the last step to the two end products acetoacetate and fumarate in catabolism. Succinylacetone, succinylacetoacetate and maleylacetoacetate Instead formed, these faulty products of metabolism ultimately lead to cell damage in liver, kidney and brain. The mutation is rare overall, and about one in 100,000 newborns is affected by the disease.

Depending on the severity of the enzyme defect, a distinction is an acute and a chronic form. The acute form manifests several months after birth. Affected infants show an enlarged liver, edema, and a general failure to thrive. The acute form of the disease, untreated, leads to death within a few months.

In the chronic form of a residual activity of the enzyme is present, so that the clinical course of the disease is milder. The condition leads in the course of chronic liver injury to cirrhosis, often at a tubal kidney damage and often neurological deficits. A third of patients develop hepatocellular carcinoma. If left untreated, it usually results in up to 10 years for death of patients.

Diagnosisch the disease is possible even when asymptomatic infant on the presence of succinyl acetone in the urine. The plasma levels of tyrosine are usually only slightly increased in type I to moderate.

Since the mid- 90s is nitisinone ( NTBC ) available as a drug for the treatment of tyrosinemia type 1. The drug blocks the degradation of tyrosine, so apply and the less toxic degradation products. In this case, however, the metabolic status of the patient is inevitably changed so much that he shows symptoms of tyrosinemia type II. Thus, the treatment with a diet tyrosinarmen must be combined in order to avoid these side effects. Blood levels of tyrosine should be below 600 micromol / l. The prognosis under proper therapy is considered to be good.

As a last therapeutic option available liver transplantation, possibly combined with a kidney transplant is available.

Tyrosinemia type II

This form of the disease is also known as oculo - cutaneous tyrosinemia, because it causes symptoms to the eyes and skin. Basis it is a mutation of tyrosine aminotransferase, which is localized in the cytosol of liver cells. The disease causes the eyes to produce corneal damage, which manifest themselves first in photophobia and increased lacrimation. During scarred the cornea and it can cause permanent vision problems arise. On the skin of the enzyme defect causes blisters and crusting on the soles and palms. This eventually go into hyperkeratosis. In addition, have about 60% of those on neurological deficits. These include primarily speech and incoordination. Less commonly you may also have self-destructive tendencies.

Characteristic of the type II tyrosinemia is the greatly increased levels of the amino acid in the blood. It can be increased up to ten times the normal value.

Treatment consists of a diet containing as little tyrosine and phenylalanine. At first, it should be resorted to special food that does not contain these two amino acids. Later can be converted to a generally low-protein diet. The plasma levels of tyrosine should be kept below 800 micromol / l. The prognosis of the disease in a strict diet is considered good.

Tyrosinemia type III

This form of the metabolic disorder is very rare, only a few cases have been reported worldwide. Its cause is dysfunction of 4- Hydroxyphenylpyruvate dioxygenase, which is caused by a mutation. Characteristic of the disease is a mild mental retardation, epileptic seizures, and intermittent ataxia.