Tyrosinemia
| Classification according to ICD-10 | |
|---|---|
| E70.2 | Tyrosine metabolism disorders Tyrosinemia |
| ICD-10 online (WHO version 2019) | |
As Tyrosinaemia refers to a group of rare, autosomal - recessive inherited, genetic metabolic disorders in which the metabolism of the amino acid tyrosine is disrupted. They have in common an increased level of tyrosine in the blood. Depending on the underlying enzyme defect, a distinction is made between three types of disease, which differ in their severity and prognosis.
Type I tyrosinemia
- see also: main article tyrosinemia type I
This form is also known as hepatorenal tyrosinemia , as it damages liver, kidneys and brain in the full picture of the disease. The disease is based on a mutation on chromosome 15. The mutation causes a deficiency of the enzyme fumarylacetoacetase , which catalyzes the last step in the breakdown metabolism to the two end products acetoacetate and fumarate . Instead, succinylacetone, succinylacetoacetate and maleyl acetoacetate are formed; these defective metabolic products ultimately damage cells in the liver, kidneys and brain. Overall, the mutation is rare, affecting around 1 in 100,000 newborns.
Depending on the extent of the enzyme defect, a distinction is made between an acute and a chronic form. The acute form manifests itself a few months after birth. Affected infants have enlarged liver , edema and general failure to thrive. The acute form of the disease leads to death within a few months if left untreated.
In the chronic form, there is residual activity of the enzyme, so that the clinical course of the disease is milder. In the course of chronic liver damage, the disease leads to cirrhosis of the liver , often to tubular kidney damage and often to neurological deficits. A third of patients develop hepatocellular carcinoma . If left untreated, it usually leads to patient death up to the age of 10.
The disease can already be diagnosed in asymptomatic infants by detecting succinylacetone in the urine. The plasma levels of tyrosine are usually only slightly to moderately increased in type I.
Nitisinone (NTBC) has been available as a drug for the treatment of type 1 tyrosinemia since the mid-1990s . The active ingredient blocks the breakdown of tyrosine so that less toxic breakdown products are produced. However, this inevitably changes the patient's metabolic situation to such an extent that he shows symptoms of type II tyrosinemia. The treatment must therefore be combined with a low-tyrosine diet in order to avoid these side effects. The blood level of tyrosine should be below 600 μmol / l . The prognosis with appropriate therapy is assessed as good.
Liver transplantation , possibly combined with kidney transplantation, is available as a final therapeutic option .
Tyrosinemia Type II
This form of the disease is also known as ocular-cutaneous tyrosinemia because it causes symptoms in the eyes and skin. It is based on a mutation of the tyrosine aminotransferase , which is located in the cytosol of the liver cells . The disease causes damage to the cornea in the eyes , which first manifests itself in photophobia and increased tear formation. As the disease progresses, the cornea scars and permanent visual disturbances can develop. On the skin, the enzyme defect causes blisters and crusts to form on the soles of the feet and palms. These eventually turn into hyperkeratosis . In addition, around 60% of those affected have neurological deficits. These primarily include language and coordination disorders. Self-destructive tendencies can appear less often.
Synonyms are: Richner-Hanhart syndrome ; Oculocutaneous tyrosinemia; Palmoplantar keratosis - corneal dystrophy; Tyrosinemia due to TAT deficiency; Tyrosinemia due to tyrosine transaminase deficiency.
Type II tyrosinemia is characterized by the greatly increased level of the amino acid in the blood. It can be increased up to ten times the normal value.
Therapy consists of a diet that contains as little tyrosine and phenylalanine as possible . In the beginning, you should use special foods that do not contain either of these two amino acids. You can later switch to a generally low-protein diet. The plasma level of tyrosine should be kept below 800 μmol / l . The prognosis of the disease with a strict diet is assessed as good.
Tyrosinemia type III
This form of metabolic disorder is very rare; only a few cases have been described worldwide. It is caused by a malfunction of the 4-hydroxyphenylpyruvate dioxygenase, which is caused by a mutation. The disease is characterized by mild mental retardation, epileptic seizures, and intermittent ataxia .
Individual evidence
- ^ A b c d e Anthony Killeen, Emanuel Rubin, David Strayer: Developmental and Genetic Diseases. In: Raphael Rubin, David Strayer: Rubin's Pathology. 5th edition. Philadelphia 2008, ISBN 978-0-7817-9516-6 , p. 213.
- ↑ a b c d e f g Tyrosinemia Type I guideline of the German Society for Child and Adolescent Medicine.
- ↑ Tyrosinemia type 2. In: Orphanet (Rare Disease Database).
