Tyrosinemia type 1

Tyrosinemia type 1 is a severe genetic disorder that manifests during the first six months of a patient’s life.

Due to an inherited genetic defect, people with this disease cannot fully break down the amino acid tyrosine, which causes an accumulation of one of the toxic metabolites created during the breaking down of this amino acid.

When left untreated, the accumulation of this metabolite in the liver and kidneys can cause hepatic failure and kidney failure. Newborn screening for this disease is available in many countries. The average prevalence of this disorder is 1 in 100,000 births.


What is tyrosine?

Tyrosine is an amino acid naturally found in various foods, especially high-protein foods, such as fish, peanuts, chicken, bananas, avocado, and soy products.

Tyrosine plays an important role in several physiological processes. It is a component of the hormone thyroxine, and an essential component in the production of neurotransmitters such as catecholamine, dopamine, and more.

Despite its important role, tyrosine is considered a nonessential amino acid. This means that our body can synthesize it from another amino acid, called phenylalanine, using an enzyme called phenylalanine hydroxylase.


Why can’t tyrosinemia patients break down tyrosine?

Normally, our body contains an enzyme called fumarylacetoacetate hydrolase. This enzyme is encoded by the gene FAH. mutations in the FAH gene cause a deficiency in this enzyme production which disrupts the final stage of amino acid metabolism.

In the past, treatment was based on decreased protein consumption, but since protein is essential for growth, finding the right balance between preventing the disease’s deterioration and assisting children in achieving their growth potential, proved difficult.

In addition, the primary treatment is a liver transplant, but with timely treatment at early stages of life, damage to the liver can be prevented.



Today, tyrosinemia is treated with prescribed NTBC, also known as nitisinone. This enzyme inhibitor is highly effective in inhibiting tyrosine breakdown. This prevents the production of the toxic metabolite created during the amino acid breakdown.

NTBC prescription to patients began in clinical trials in 1991. Since then, hundreds of patients were successfully treated. Around 90% of patients enjoyed a dramatic improvement in their condition following this treatment and only 10% did not respond to this drug therapy.

It should be noted that lately, suspicions were raised that long term NTBC use may cause negative side-effects such as cataracts – clouding of the lens of the eye.



Initial symptoms vary between patients. In some babies, symptoms include diarrhea and vomiting, and in others, symptoms include an enlarged spleen (splenomegaly) and enlarged liver (hepatomegaly). This leads to hepatic failure, kidney failure, and an increased risk for liver cancer.

Besides tyrosinemia type 1, the disease has two other forms: tyrosinemia type 2 (type II) which occurs in 1 in 250,000 births, and type 3 (type III) which is even rarer with only few cases reported.

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