Tyrosinemia

Tyrosinemia

Tyrosinemia is characterized by increased blood concentrations of the amino acid tyrosine. All forms of the disease have genetic causes. Type I tyrosinemia in particular leads to early death if left untreated.

What is tyrosinemia?

Tyrosinemia is a genetically determined breakdown disorder of the amino acid tyrosine, which leads to an increase in the tyrosine concentration in the blood. To date, three different forms of tyrosinemia are known. They differ causally in the location of the disruption in tyrosine degradation. All three forms of tyrosinemia are characterized by an increased concentration of tyrosine and phenylalanine to varying degrees:

  • In tyrosinemia type I, toxic degradation products are also formed in the body because the normal degradation pathway is blocked by an enzyme defect at the end of the degradation chain. These defective products of tyrosine degradation are toxic to the liver and kidneys, so that type I tyrosinemia takes a particularly severe course.
  • Type II tyrosinemia is mainly characterized by increased levels of tyrosine and phenylalanine with all their effects on the eyes, skin and nervous system. Here, the degradation of tyrosine is already blocked at the beginning of the degradation chain.
  • The mildest and rarest form of tyrosinemia is tyrosinemia type III. The tyrosine and phenalalanine concentrations are less elevated here. However, the increased concentrations have effects on the nervous system. In general, tyrosinemias are very rare. In tyrosinemia type I, cicra one to two per 100,000 people are affected. Only a few cases of tyrosinemia type III have been described.

Causes

The general cause of all three forms of tyrosinemia lies in the disruption of tyrosine degradation by defective enzymes. The form of the disease depends on the affected enzymes in the tyrosine catabolism chain. All tyrosinemias are caused by autosomal recessive mutations. For what does the abbreviation lgs stand for, please visit usvsukenglish.com.

In tyrosinemia type I, the enzyme fumarylacetoacetate hydrolase is largely inoperative. Its coding gene is located on chromosome 15. This enzyme is responsible for the last step in the tyrosine breakdown chain. Normally, the intermediate products fumarylacetoacetate and maleylacetoacetate are degraded in this reaction step.

However, when the enzyme is defective, these metabolites accumulate and are then converted to succinylacetoacetate and succinylcholine in an alternative reaction. However, these substances are strong liver and kidney toxins. Depending on how high their concentration in the blood is, they lead to the complete destruction of the liver and kidneys either quickly or via a chronic process.

Type II tyrosinemia is caused by a defect in the enzyme tyrosine aminotransferase. This enzyme initiates the first step in tyrosine degradation. When it fails, tyrosine accumulates more and more in the blood. The concentration can be increased up to ten times the normal value. Since tyrosine is formed from the amino acid phenylalanine, the phenylalanine concentration also increases at the same time. Elevated levels of phenylalanine are known to damage the nervous system.

At the same time, the high tyrosine levels attack the eyes and skin. Finally, type III tyrosinemia is caused by a defect in the enzyme 4-hydroxyphenylpyruvate dioxygenase. The tyrosine and phenylalanine levels are only slightly increased here. Due to the blockade in the tyrosine degradation chain, a backlog of tyrosine develops in all three forms of tyrosinemia, which is of course more pronounced the closer it is to the beginning of the degradation chain.

Symptoms, Ailments & Signs

Type I tyrosinemia is characterized by damage to the liver, kidneys and brain. The disease is already evident in newborns through poor drinking, vomiting, liver disease and renal insufficiency. There are two forms, both of which lead to early death from liver and kidney failure if left untreated.

In the fulminant form, liver enlargement, edema and severe growth disorders occur early on. Death occurs within a few months of birth. In the milder form, the liver and kidneys are chronically degraded. Cirrhosis of the liver develops over a long process, which often also leads to liver cancer.

If left untreated, death occurs by the age of ten at the latest. In tyrosinemia type II, damage to the cornea of ​​the eyes, formation of blisters and crusts on the skin and various neurological deficits occur. Type III tyrosinemia is characterized by mild mental impairment, impaired motor coordination, and epileptic seizures.

Diagnosis & course of disease

Tyrosinemia can be diagnosed by various blood and urine tests. Elevated tyrosine levels are detected in urine samples . Furthermore, the toxic metabolites such as succinylacetone can also be detected in the urine in type I tyrosinemia.

Complications

Depending on the type, tyrosinemia can cause various complications. Type I tyrosinemia can cause symptoms such as poor drinking, liver disease and kidney failure due to congenital liver, kidney and brain damage. The lack of drinking can lead to dehydration and, as a result, to dehydration relatively quickly.

Liver diseases always have serious effects on the whole body and can cause, for example, jaundice and severe inflammation of the internal organs. Kidney failure is just as serious because if left untreated, it can lead to kidney failure and death. In the fulminant form, tyrosinemia can also promote growth disorders, edema and liver cancer as well as liver cirrhosis.

Type II tyrosinemia is associated with corneal damage, neurological deficits and other complications. In the course of the disease, type III tyrosinemia can cause epileptic seizures, impaired movement coordination and mental impairment. In the treatment of the breakdown disorder, the complications depend on the respective measure and the constitution of the patient.

The typically prescribed nitisinones can cause migraines and other side effects. A liver transplant always carries the risk that the body will reject the organ. Infections and wound healing disorders can also occur.

When should you go to the doctor?

The person affected should always consult a doctor with tyrosinemia to prevent further complications or upsets. Early detection with subsequent treatment is very important, so that the affected person should consult a doctor at the first signs and symptoms of the disease. In the worst case, the child can die from tyrosinemia. The doctor should be contacted for this disease if the child suffers from severe jaundice or diarrhea. Internal bleeding can also indicate this disease. Poisoning of the liver and other internal organs is also evident.

An increased heart rate or abnormal sensations in different parts of the body often indicate the disease and should be checked by a doctor. Paralysis can occur anywhere in the body. Tyrosinemia should be treated promptly by a pediatrician or in a hospital. The further course depends on the time of diagnosis, so that no general prediction can be given. The life expectancy of the child may also be reduced as a result of this disease.

Treatment & Therapy

All forms of tyrosinemia are positively influenced by a diet low in tyrosine and phenylalanine. In the case of tyrosinemia types II and III, such a diet can reliably improve the symptoms. However, treating tyrosinemia type I is much more difficult. In addition to a strict diet, the formation of toxic metabolites must also be prevented.

This can be achieved by the drug nitisinone (NTBC) by blocking an earlier step in degradation. This increases the tyrosine concentration in the blood. However, this can be kept low by the diet. Liver transplantation should be considered in advanced hepatic insufficiency.

Prevention

Since tyrosinemias are genetic, they cannot be prevented. However, with a strict diet low in tyrosine and phenylalanine, at least patients with type II and III tyrosinemia are able to lead a largely normal life. In patients with type I tyrosinemia, levels of metabolites, tyrosine, and phenylalanine must be regulated lifelong by drug treatment and strict diet.

Aftercare

Tyrosinemia is an inherited metabolic disorder. It is considered a rare disease and is classified using the three forms I, II and III. The treatment options depend on the form. Appropriate follow-up care is necessary to achieve a favorable prognosis. The patient should be able to live as unrestricted a life as possible.

In type II tyrosinemia, dietary treatment is often sufficient. However, the doctor’s orders must be followed exactly. The healing process is checked during aftercare, which is scheduled for the medium to long term. Type III tyrosinemia is the rarest form of the metabolic disease. It is associated with mild mental impairment and epilepsy.

During follow-up care, those affected and their families learn how to deal with the disease on a day-to-day basis. Special follow-up care is necessary for complete type I disease. If left untreated, this tyrosinemia can be life-threatening. Internal organs such as the kidneys or the brain are damaged. An unfavorable course requires lifelong follow-up care.

Organ transplants may be a possibility at the doctor’s discretion. It is considered when other measures no longer help. Follow-up care is carried out in the clinic, the patient’s condition is closely monitored. Regular checks provide information on the compatibility of the new organ. Rejection reactions of the body must be avoided.

You can do that yourself

Depending on the type of disease, tyrosinemia patients may adopt various dietary measures to support conservative management. In tyrosinemia type I, a high-energy diet is important. The diet should produce as little tyrosine as possible in the body. Catabolic situations, such as those that occur after prolonged starvation, should be avoided by eating regularly. The consumption of milk, egg and meat products should be severely restricted. The diet can slow the progression of the disease. It should be created together with a doctor and a nutritionist and implemented consistently.

Type II tyrosinemia can also be treated with an appropriate diet. In tyrosinemia type III, preparations for medical emergencies must be made in addition to dietary measures. In the event of an epileptic seizure, first aid measures should be initiated by calming the patient and administering rescue medication. The affected person must be placed in the stable side position so that he/she does not injure himself or fall on objects and also so that no vomit enters the trachea. Possible consequences of an ataxia can be treated by physiotherapybe prevented. Stairs, thresholds and dangerous objects in the household must be secured to minimize the risk of injury from falls. The exact measures for type I, II and III tyrosinemia should be discussed with a specialist.

Tyrosinemia