Additional information about Tyrosinaemia type 1 and treatment

What is Tyrosinemia type 1?

Tyrosinemia type 1 is a very rare, but severe, inborn error of metabolism or metabolic disease. Most metabolic diseases are caused by a defect in the production, conversion, or degradation of nutritional products in the body. In this case, when someone has Tyrosinemia type 1, the amino acid tyrosine can’t be metabolized normally.

So why is it called Tyrosinemia type 1? This suggests that there should be other types of Tyrosinemia as well. Well, this is correct. Tyrosinemia type 2 and 3 also exist. Normally, tyrosine is metabolized in several distinctive steps. Something can go wrong at any of these steps leading to different types of Tyrosinemia. All kinds of Tyrosinemia have their own clinical symptoms and treatment.

From now, we will only be discussing Tyrosinemia type 1.

Where is tyrosine coming from?

In Tyrosinemia type 1 patients, tyrosine can’t be metabolized or degraded normally. Tyrosine in your body comes from all kinds of food that contain at least some amount of protein. Tyrosine is namely an amino acid, one of the building blocks of protein you eat. Alternatively, the body can also produce tyrosine by the degradation of another building block, namely phenylalanine. Last but not least, when proteins in your body are degraded, the building blocks, including tyrosine, will be released. To conclude, your body can get tyrosine in three different ways: 1. By eating protein containing food, 2. By metabolizing phenylalanine into tyrosine, 3. By degradation of proteins in your body that releases the building blocks, including tyrosine.

What is the problem in Tyrosinemia type 1?

Due to the inability to metabolize tyrosine normally, toxic products will be produced by the body. Unfortunately, we can only measure one of the toxic products well, namely succinylacetone. These toxic products, including succinylacetone, can damage various organs in your body. Among others, they can lead to severe liver failure, liver cancer, kidney problems, heart problems, pancreas problems, and neurological problems with paralysis.

How to diagnose Tyrosinemia type 1?

In the past, Tyrosinemia type 1 was diagnosed only when patients arrived in the hospital, usually while suffering from various kinds of problems (for example: growth problems, nausea and vomiting, bleeding, enlarged liver, drowsiness, respiratory problems, acute abdomen pain, walking problems, or paralysis). Further investigation in the hospital then revealed problems such as liver failure, liver cancer, heart problems, pancreas problems, kidney problems and/or neurological problems. In this case, a special investigation is sometimes done to diagnose if someone is suffering from Tyrosinemia or not, but of course with so many diverse symptoms, it is not always easy to recognize especially as it is a very rare disease.

Nowadays, in some countries (among which is the Netherlands) almost all newborns are screened with the neonatal heel prick (also referred to as the Guthrie test) for having Tyrosinemia. Some small drops of blood are taken from the newborn’s heel shortly after birth and analysed in a screening laboratory. In this way, Tyrosinemia type 1 can be diagnosed before severe symptoms arise. Severe, life threatening problems can be prevented when treatment is initiated this early.

How to treat Tyrosinemia type 1?

Nowadays, the treatment of Tyrosinemia type 1 consists of two different parts: a drug called NTBC or Nitisinone (Orfadin®) and a special diet.

The drug NTBC makes sure that the toxic products that previously characterized the disease are not formed. Due to NTBC, most of the clinical problems do not occur or can be treated effectively. Two issues should be mentioned. Some patients may need liver transplantation if NTBC is not started in time. If NTBC is not started before the age of 2-3 months, the risk of liver cancer is higher. The combination of neonatal screening and NTBC greatly improves patient outcomes and survival. However, the administration of NTBC results in increased tyrosine concentrations higher than what is seen in normally. These high tyrosine concentrations can be dangerous to the eyes, skin and may adversely affect brain function. Therefore, NTBC treatment also includes reducing tyrosine concentrations. Since tyrosine is present in protein-rich foods, tyrosine concentrations can be lowered by following a special diet, specifically by avoiding its precursor phenylalanine. With this special phenylalanine-tyrosine restricted diet, a patient taking NTBC can avoid high levels of tyrosine.

The phenylalanine-tyrosine restricted diet consists of several parts. People with Tyrosinemia type 1 are not allowed to eat or drink protein-rich food. Thus, the intake of tyrosine and its precursor phenylalanine is limited by eating less natural proteins such as in pasta, bread, fish, and dairy products. However, in this way, the intake of other amino acids is also limited. People with Tyrosinemia type 1 also take a special amino acid mixture. This mixture contains all the amino acids the body needs except for phenylalanine and tyrosine. Unfortunately, patients sometimes get too little nutrients due to avoiding protein-rich foods.