What is Tyrosinemia?

Types of Tyrosinemia

​Tyrosinemia refers to a group of genetic disorders that prevent the breakdown of the amino acid tyrosine. 

There are four types of tyrosinemia:

• Transient (temporary) Tyrosinemia

• Tyrosinemia Type I

• Tyrosinemia Type II

• Tyrosinemia Type III

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All types of tyrosinemia can cause an increase in blood tyrosine levels. Transient Tyrosinemia is a temporary condition that can occur in newborns that usually improves over time, although it is best to consult a physician to manage this temporary condition. The other three types of tyrosinemia are considered life-long conditions that are treated and managed by metabolic disease experts.

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Tyrosinemia type I, II, & III are enzyme deficiency disorders caused by single gene defects. Dysfunction at one of the sequential enzymatic reactions of the tyrosine breakdown pathway will lead to the accumulation of toxic metabolites.

Tyrosinemia Type I is caused by a defect in the FAH gene that encodes the fumarylacetoacetase (FAH) enzyme. This disease, can be identified by measurement of an unusual chemical compound (succinylacetone) in the blood via newborn screening and early treatment can prevent many complications. This disease is treated with medication called "nitisinone", a low protein diet, and medical food under the guidance of a dietician. 

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Tyrosinemia Type II is caused by a defect in the TAT gene that encodes the tyrosine aminotransferase (TAT) enzyme. This disease affects the eyes and skin, but can be managed with a low protein diet and medical food.

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Tyrosinemia Type III is caused by a defect in the HGD gene, which encodes the 4-hydroxyphenylpyruvate dioxygenase (HGD) enzyme. This is the rarest form of tyrosinemia, and it can also be managed with low protein diet and medical food. 

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All non-transient forms should be managed by a team of metabolic disease specialists who will monitor growth and development. These specialists base all treatment decisions on the latest guidelines to optimize brain development and reduce complications related to toxic metabolites that can accumulate in the blood.

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How is tyrosinemia detected and treated?

Newborn screening (heel-stick blood draw) is essential to detect all forms of tyrosinemia, including the transient form of the disease. The transient form is detected most frequently in premature infants, and usually resolves after 2 months of age. It is characterized by elevated tyrosine (and sometimes elevated phenylalanine) in the blood. If your baby’s newborn screening result for tyrosinemia was above the normal range, your baby’s doctor will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has a life long condition. An out-of-range result may occur because the initial blood sample was too small, the test was performed too early, or may be due to Transient (temporary) Tyrosinemia. It is very important that you go to your follow-up appointment for a confirmatory test to determine the cause.

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Tyrosinemia Type I is detected on newborn screening if the most accurate test (succinylacetone measurement) is used to screen the heel stick blood. Measurement of tyrosine alone is often not sensitive enough to detect Tyrosinemia Type I. Measurement of succinylacetone is the most accurate way to identify Tyrosinemia Type I in a newborn. Early detection of Tyrosinemia Type I is critical, since it is considered the most severe form of Tyrosinemia. If not detected early and treated with nitisinone, diet, and medical food, Tyrosinemia Type I can result in neurologic crisis, liver failure, liver cancer, renal damage, and other severe complications. If treated early and managed well, children with Tyrosinemia Type I can lead much healthier lives.

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Tyrosinemia Type II and Type III are both detected on newborn screening by elevations in blood tyrosine. Both are treated by managing blood tyrosine levels with a low protein diet and medical food. A dietician works with the families at every stage of growth and development to optimize health and well-being for the child and family. 

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What happens if tyrosinemia is not treated?

All non-transient forms of Tyrosinemia can affect growth and development of a child when not managed correctly. Early intervention is essential so that the best outcome for your child and the well-being of the family can be optimized. It is difficult to hear that something might be wrong with your child, but it is essential that parents follow-up with their healthcare providers as soon as possible if an abnormal result is identified on newborn screening. All types of Tyrosinemia can be treated and managed. You are not alone, there are other families and health care providers to support you. Please contact us if you have questions or concerns.

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