Disease

 Tyrosinemia Type 1

a rare, inborn metabolic error disease

Tyrosinemia type 1 is a rare, inborn metabolic error disease. With metabolism, the nutrients are in charge and toxins are disposed of. Enzymes are very important in this process. If something is wrong with an enzyme, it accumulates in the body and there is a metabolic disease.

Patients with Tyrosinemia type 1 have problems breaking down the Tyrosine (a part of protein), which is caused by a fault in the enzyme fumarylacetoacetate hydrolase.

Normally, Tyrosine is broken down in the liver and also in the kidneys. Due to the fault in the enzyme, the toxic fumarylacetoacetate is accumulating and causing damage to the liver and kidneys. Without treatment, the patients will die.

It’s very important to diagnose Tyrosinemia as soon as possible after birth. Then, the treatment can be started immediately making the chances of long-term damage smaller. Tyrosinemia is an inborn error. If both parents are carriers, there is a 25% chance that the child will have Tyrosinemia.

Neo-natal heel prick

For a few years now, Tyrosinemia type 1 has been part of the ‘neo-natal heel prick’ in The Netherlands. Some drops of blood are taken 3 to 5 days after birth from the newborn’s heel. Within one week of the birth, you will know if the baby has Tyrosinemia, or one of the other 32 diseases that are part of the screening test in The Netherlands.

However, the neo-natal heel prick for babies is not available everywhere in the world, and if it is, Tyrosinemia is not always included in the screening.

How to treat Tyrosinemia?

Most Tyrosinemia patients live in developed countries: Europe, Canada, USA and Australia. In addition, there are some cases in South America and the Middle East. Many Tyrosinemia patients died in the past because only following a low-protein-diet was (and still is) insufficient.
Placing the drug Nitisinone on the market, (which was discovered by accident), gives a much better outlook for Tyrosinemia patients. 
This drug is sadly not available worldwide, and is not affordable for everyone.

Medication

The treatment of Tyrosinemia type 1 is very different around the world. Even in Europe, the treatments are different. In The Netherlands, the treatment consists of the drug Nitisinone, supplements and a low-protein diet. In most cases, phenylalanine is also added. In The Netherlands, you can get Nitisinone, phenylalanine and the supplements free on prescription, from the metabolic paediatrician.

Until November 2016, Nitisinone or Orfadin R was only available from the Swedish producer SOBI. For 25 years, SOBI had a monopoly position producing Nitisinone.

Currently, two more manufacturers are producing Nitisinone. The Canadian productionucer MendiliKABS, provides Nitisinone MDK in Canada and in almost all European countries. The British producer Cycle pharma, provides Nityr (Nitisinone) in Canada, USA, Australia and Chile. At the moment, the manufacturer SOBI still has the biggest market share.
Although two more manufacturers are on board, Nitisinone is still NOT available worldwide and for everyone. For the Tyrosinemia Foundation, this is a huge area of concern.

Low protein diet and supplements

Secondly, the treatment of Tyrosinemia type 1 includes a low-protein diet, to reduce the intake of the amino acid Tyrosine. For the Tyrosinemia patient, it is very important to know the quantity of Tyrosine in food. For the majority of foods, this is unknown – therefore for Tyrosinemia type 1 patients, means this a low-protein-diet. Because of the resulting low-protein-diet the intake of all 20 amino acids is poor.

Amino acids are very important nutrients that ensure growth and development of muscles, bones, hormones and antibodies.
To boost this shortage, patients need supplements. Patients with Tyrosinemia type 1 have to take supplements 3 times a day (toddlers 5 times daily) with their allowed food, to obtain a basic balanced diet.

It varies in every country in the world if low-protein products are available. If they are available, it depends upon where you live if the government or insurance reimburses you. For example in Germany, The Netherlands and Scandinavian countries, you have to pay yourself for the low-protein products as flour, spaghetti and snacks.

In Belgium, United Kingdom, France, Italy, Spain and Turkey the patients get their low-protein products from the pharmacies and they are paid for by the government. In Romania and Russia, the patients have to import the low-protein products by themselves.

Futhermore, the medical checks for Tyrosinemia type 1 patients are different in every country and also depend upon which metabolic paediatrician you are visiting.

In 2013, recommendations for the management of Tyrosinemia type 1 were published. These were based on medical knowledge, publications and unpublished research. All together there was insufficient justification to make the guidelines. This is the reason why it produced recommendations: author Corinne de Laet, published in Orphanet January 2013 ojrd.biomedcentral.com. 
The Tyrosinemia Foundation is committed to getting European Guidelines published. Check out our campaign.
 When the European Guidelines are live, we will go for the Worldwide Guidelines.

Low-protein in reality

Nearly all foodstuffs contain protein – vegetables, fruit, cereals, dairy products, meat and fish. The amount of natural protein intake during the day depends on the mutation on the gene. There are patients who can only have 8 grams (1 big boiled egg) of natural protein intake and there are also patients who can have 40 grams of natural protein intake to obtain a healthy balance. That’s why it is essential to know how much protein is in the food (product) so every patient can monitor their intake.

Generally, a low protein diet means: vegetables, fruit and additional low-protein manufactured products. NO meat, fish, soya, nuts, dairy products and ‘normal’ flour or pasta.

Have a look at the following website to see how much protein is found in certain foods
Food protein list

Besides counting protein, planning is an essential daily activity that the parents (and as they get older – the children) have to undertake. The structure and planning is all about balancing the intake of medication, supplements and following a low-protein diet.

Medical information

mother Annelies:

‘We always think in possibilities!’

When we were first informed about Tyrosinemia, our lives turned upside down. I thought, how we will survive?
Initially, we only saw the restrictions of a low-protein diet. You feel like you have the weight of the world on your shoulders. As we went along, we learned more about counting proteins.

The protein content differs in every type of food and that is why you have to plan seriously. Our son, Joris (aged 13), can have 8 grams of natural protein intake to stay healthy. This is the same as one big boiled egg.

In the beginning, we weighed everything and were always counting the protein content. Nowadays, we know the amount of protein of the frequently used products and we also follow our instincts. Planning is necessary each day - this is a big effort. The planning is about the 2 times a day intake of medicines, 3 times a day intake of supplements, in combination with planning the food and meals for the day.

“What will we have for dinner?” “How many proteins?” “Are the products available?” “ Which snacks he will take to school?” That takes time and generally, I have to cook two different meals. Joris is 13 years old and I noticed that at all age stages, new things are coming. Good planning and coordination with your child and their surroundings (school/sport/friend/party) remains very important. The nice thing is, you can grow and add things gradually.

Joris goes to his friends houses and he has sleepovers. As a family, we regularly go on holiday. All is possible, and for all activities, I organise the medication, supplements and a big part of the menu in advance. We want Joris to be the same as other children. In doing so, it helps us to always think in possibilities and not in restrictions!

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