"Tyrosinemia Type 1" – What Is It?
Tyrosinemia type I is a metabolic disease caused by mutations, i.e., genetic changes in the FAH gene. If left untreated, it usually leads to acute liver failure, impaired kidney function with growth disorders and rickets (a disease of the growing bones caused by vitamin D deficiency), as well as neurological crises within the first year of life. Without adequate treatment, the disease is fatal within the first ten years of life. However, with treatment with nitisinone and adherence to a diet low in tyrosine, the survival rate is over 90%.
How Is "Tyrosinemia Type 1" Diagnosed?
Suspected Diagnosis
Type I Tyrosinemia is suspected if the following findings are present:
- Elevated tyrosine levels in newborn screening
- Severe liver disease in young infants
- Signs of kidney disease, rickets, and/or neurological crises in children >6 months of age
Laboratory Chemical Diagnostics
- Increased concentrations of certain metabolic products in the blood and urine
- Impaired coagulation values as a sign of liver dysfunction in untreated tyrosinemia type I
Genetic Diagnostics
The diagnosis of “tyrosinemia type I” is confirmed when a mutation, i.e., a genetic change in the FAH gene, is detected.
What Is the Risk of Cancer?
A basic distinction must be made between patients receiving early and adequate treatment and those not.
Children with untreated tyrosinemia type I have a significantly increased risk of liver cancer (hepatocellular carcinoma). Inadequately treated children (i.e., children who were started on nitisinone therapy before the age of 2), the risk of hepatocellular carcinoma is < 5% up to the age of 10.
In addition to the increased risk of cancer, other clinical manifestations may occur in the context of tyrosinemia type I. Here, too, a distinction should be made between treated and untreated disease.
Untreated Tyrosinemia Type I
Children with tyrosinemia type I who are not detected in newborn screening usually present in early infancy with severe liver involvement or later in the first year of life with liver dysfunction, kidney involvement, growth failure, and rickets. If left untreated, tyrosinemia type I leads to death within the first ten years of life.
- Liver involvement:
If undiagnosed and untreated, tyrosinemia type I typically leads to acute liver failure within the first 6 months of life. Initially, the liver can no longer produce clotting factors, which can lead to a clinical blood clotting disorder with increased or prolonged bleeding. Other liver values (transaminases and bilirubin) are usually only slightly elevated, an unusual constellation distinguishing tyrosinemia type I from other severe liver diseases. - Kidney involvement:
In untreated children, kidney involvement usually only becomes apparent after the sixth month of life in the form of impaired renal tubule function. This leads to increased amino acid excretion and a loss of phosphate, which can cause rickets, as well as incorrect acid excretion via the kidneys. - Neurological crises:
Neurological crises can occur repeatedly in untreated children. These manifest themselves with symptoms such as behavioral changes, abdominal pain, damage to the peripheral nerves, and respiratory disorders, including the need for ventilation.
Treated Tyrosinemia Type I
The combination of nitisinone therapy and tyrosine-reduced diet leads to a survival rate of >90%, normal growth, improved liver function, prevention of liver cirrhosis, improved kidney function, and prevention of rickets.
- Neurological crises:
These were only observed in patients with prolonged treatment interruption. - Liver involvement:
Acute liver failure usually improves within the first week after starting nitisinone therapy.
What Is Known About the Development of "Tyrosinemia Type 1"?
Tyrosinemia Type I is caused by mutations, i.e., genetic changes in the FAH gene. This gene codes for the FAH protein, which is necessary for the final step in breaking the amino acid tyrosine.
If the FAH gene is present in an altered form, the FAH protein is also not produced correctly and can no longer fulfill its actual function. As a result, tyrosine is broken down incorrectly, causing various metabolic products to accumulate. This leads to damage to the liver, kidneys, and nerves.
Tyrosinemia Type I occurs in around one in 100,000-120,000 people. It is significantly more common in Scandinavia, Finland, and Quebec (Canada). It can be passed on from parents to their children, whereby the inheritance is autosomal recessive.
Is There Any Form of Treatment Available?
Nitisinone therapy should be started immediately after diagnosis. In addition, a low tyrosine diet must also be followed from the time of diagnosis.
If there is no response to nitisinone therapy or malignant changes in the liver, a liver transplant may be considered.
Diagnosis of " Tyrosinemia Type 1" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " Tyrosinemia Type 1" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Due to the increased risk of hepatocellular carcinoma, the following screening tests should be carried out:
- Monthly determination of AFP (alpha-fetoprotein) for the first 6 months of life
- After the 6th month of life, determination of AFP every 6 months
- An ultrasound examination or MRI of the liver can be considered as basic diagnostics.
Tyrosinemia Type 1 – What You Can Do Yourself
You Should Pay Attention to This
It is particularly important for patients with tyrosinemia type I to receive uninterrupted nitisinone therapy and to consistently adhere to a diet low in tyrosine.
You should consult a doctor as soon as you experience increased or prolonged bleeding, increased drowsiness, or difficulty drinking. However, non-specific symptoms such as abdominal pain should also be noted and reported to a doctor. You should also consult a doctor if you experience new abnormalities or complaints.
Further Information
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