Type I Tyrosinemia

Type I Tyrosinemia

Type I tyrosinemia is a congenital metabolic disease. It only occurs very rarely.

What is Tyrosinemia Type I?

Type I tyrosinemia belongs to the group of tyrosinemias. It is also known as type I hypertyrosinemia or hepato-renal tyrosinemia. The rare congenital metabolic disease occurs in one in 100,000 newborn children. Their inheritance is autosomal recessive. A defect in an enzyme results in the formation of harmful metabolites during the breakdown process of the amino acid tyrosine. This disease primarily affects the kidneys and liver. The occurrence of tyrosinemia type I is already evident in babies or small children. For what does the abbreviation lmbbs stand for, please visit usvsukenglish.com.

Causes

Type I tyrosinemia is caused by a mutation on chromosome 15. This mutation causes a deficiency in the enzyme fumarylacetoacetase (FAH or FAA). The FAH enzyme catalyzes the two end products fumaric acid and acetoacetic acid as part of the breakdown metabolism of tyrosine. However, due to the mutation, succinylacetoacetate, succinylacetone and maleylacetoacetate are produced, which cause damage to the cells in the kidneys, liver and brain.

Furthermore, the functionality of the enzyme 5-aminolevulinic acid dehydratase is impaired by the defective metabolite succinylacetone. This damages the nerves and causes attacks that resemble porphyria. The FAH gene affected by the disease is made up of 35,000 base pairs. In addition, an mRNA of 1260 base pairs is encoded. The most common mutation seen in type I tyrosinemia is a replacement of the nucleobase guanine with the nucleoside adenosine, causing the mRNA to splice incorrectly.

Symptoms, Ailments & Signs

In tyrosinemia type I, it is important to distinguish between an acute and a chronic form. When the earliest form appears, it occurs 15 days to 3 months after the birth of the affected child, with liver cell necrosis and liver failure occurring. The sick babies suffer from jaundice, diarrhea, vomiting, edema, ascites, hypoglycemia and bleeding in the gastrointestinal area. A feared complication is blood poisoning (sepsis).

Acute liver failure is the first manifestation of type I tyrosinemia in about 80 percent of all affected children. Over time, the chronic form leads to liver damage and liver cirrhosis. In addition, there is an increased risk of liver cell carcinoma. This disease usually shows up between the ages of 15 and 25 months.

Type I tyrosinemia also damages the kidneys. This is manifested by failure of the renal tubules. Damage to the renal corpuscles and the collapse of renal function are within the realm of possibility. Renal tubular acidosis and enlargement of the kidneys can also occur.

Type I tyrosinemia also results in neurological damage. The affected children suffer from increased muscle tone, painful sensations, increased heart rate and intestinal obstruction. After a short recovery period, paralysis spreads to the whole body.

Diagnosis & course of disease

In Germany, the tyrosine level in the blood is determined as part of a screening of newborn babies. However, only 90 percent of all sick children can be identified with this method. In the remaining 10 percent, the amino acid level increases later. In the USA it is also possible to determine succinylacetone, 5-aminolevulinic acid and methionine.

As part of prenatal diagnostics, the succinylacetone can be determined from the blood of the umbilical cord by performing an umbilical cord puncture. Another option is to determine the activity of the FAH enzyme within chorionic cells or amniocytes. Since tyrosinemia type I is a very rare disease, little can be said about the long-term course of the disease. If treated early, the prognosis is usually positive.

Complications

Type I tyrosinemia is a very serious disease that can, in the worst case, lead to the death of the child. In many cases, the children die a few weeks or months after birth. However, the further course depends very much on the exact severity of the disease.

Those affected suffer from acute liver failure and thus from jaundice or severe diarrhea. Type I tyrosinemia also causes vomiting or severe bleeding in the stomach or intestines and has a very negative effect on the patient’s quality of life. Most children die from liver failure for this reason.

Furthermore, there is an increased heart rate and various abnormal sensations. An intestinal obstruction can also occur due to tyrosinemia type I and, in the worst case, lead to the death of the patient. Type I tyrosinemia is treated with medication and surgery.

No general prediction can be made about the further course of the disease. However, the life expectancy of those affected is significantly reduced. The parents and relatives of the affected children also suffer from severe psychological stress and therefore also need psychological treatment.

When should you go to the doctor?

In the case of tyrosinemia type I, the affected person is dependent on treatment by a doctor. This disease cannot heal on its own, so treatment by a doctor is always necessary. Since tyrosinemia type I is a genetic disease, genetic counseling should be carried out if you wish to have children so that the disease does not recur. A doctor should be consulted as soon as the first signs and symptoms of the disease appear.

In tyrosinemia type I, the doctor should be contacted if the patient suffers from diarrhea, vomiting and jaundice. Bleeding in the stomach area can also indicate the disease. Abnormal sensations or an increased heart rate can also indicate the disease. Type I tyrosinemia can be diagnosed by a pediatrician or general practitioner. Further treatment depends on the exact severity of the symptoms. In many cases, this disease also reduces the life expectancy of those affected.

Treatment & Therapy

The drug NTBC (Nitisinone) is used to treat Type I tyrosinemia. The enzyme 4-hydroxyphenylpyruvate dioxigenase is blocked by the nitisinone. Within the tyrosine metabolism, this takes on the task of catalyzing an early degradation step. In this way, substrates that form toxic metabolites are no longer available. The drug shows a positive effect in about 90 percent of all sick babies and toddlers.

Even in the stage of acute liver failure, there is improvement. The success of the treatment can be checked by determining the succinylacetone. However, drug therapy cannot prevent the development of liver cell carcinoma. Despite therapy, liver cancer sometimes occurs . Another important part of the treatment is a special diet. Its aim is to largely prevent the formation of tyrosine in the body. For the diet, the child is given food that contains neither tyrosine nor phenylalanine.

In addition, it is high in calories. Due to the high nutritional value, it is possible to counteract catabolic states. In addition, tyrosine can no longer be released in the body through external intake. Following this special diet, the child receives normal foods that are low in tyrosine and phenylalanine. Meals are distributed regularly and in equal amounts throughout the day.

Another therapy option is a liver transplant. It is used when the NTBC has no effect on the patient, which is the case in about 10 percent of all children.

Prevention

Since tyrosinemia type I is a hereditary disease, there are no effective preventive measures.

Aftercare

In most cases, those affected with tyrosinemia type I have only a few and usually only very limited direct follow-up measures available. For this reason, they should consult a doctor at an early stage so that further complications or symptoms from this disease can be prevented. Self-healing cannot occur, so a doctor should be contacted at the first signs or symptoms.

In some cases, tyrosinemia type I can lead to infections or inflammation of the urinary tract or kidneys, so treatment with antibiotics is necessary. However, the disease cannot always be completely cured, so that the affected person may remain infertile even after the procedure.

The further course depends heavily on the time of diagnosis, so that a general prediction is usually not possible. The life expectancy of the affected person is not reduced by this disease. In some cases, contact with other people affected by the disease can be useful in order to exchange experiences and methods.

You can do that yourself

The therapy of tyrosinemia type I can be supported by dietary measures. A high-energy diet that provides the body with all the important amino acids is recommended. Adjusting the diet prevents the metabolism from mobilizing the tyrosine from the muscle tissue, which allows the metabolism to normalize relatively quickly.

The diet should otherwise be balanced and consistent. It is important to have a diet in which the metabolism does not go into a catabolic state. For this reason, as many small meals as possible should be eaten, ideally distributed evenly throughout the day. The consumption of milk, meat and egg products must be severely restricted. An important self-help measure is taking the prescribed medication, such as nitisinone, according to the doctor’s instructions.

After a liver transplant, the doctor’s instructions must be followed first and foremost. Daily weight control and eating lots of vegetables, fish and poultry is recommended. Meat, milk and dairy products should contain as little fat as possible. Fruit and especially grapefruit must be largely avoided after a liver transplant. In addition, general rules of conduct apply for the time after a liver transplant.

Type I Tyrosinemia