The condition is caused by a change in the TAT gene. This gene gives the body instructions for making the enzyme tyrosine aminotransferase. This enzyme is part of the first step in breaking down the amino acid tyrosine.

Without a working TAT gene, the body cannot break down enough tyrosine. As a result, tyrosine and related substances can build up and cause damage to the body.

Normal Function

The TAT gene provides instructions for making a liver enzyme called tyrosine aminotransferase. This enzyme is the first in a series of five enzymes that work to break down the amino acid tyrosine, a protein building block found in many foods. Specifically, tyrosine aminotransferase converts tyrosine into a byproduct called 4-hydroxyphenylpyruvate. Continuing the process, 4-hydroxyphenylpyruvate is further broken down and ultimately smaller molecules are produced that are either excreted by the kidneys or used to produce energy or make other substances in the body.

Health Conditions Related to Genetic Changes

Tyrosinemia

At least 22 TAT gene mutations have been found to cause tyrosinemia type II. This condition often affects the eyes, skin, and mental development. Most of these mutations change single DNA building blocks (base pairs) within the TAT gene. Research suggests that the altered TAT gene produces a tyrosine aminotransferase enzyme with reduced activity. Other mutations delete all or part of the TAT gene, eliminating enzyme activity. As a result of these mutations, tyrosine is not properly broken down. Tyrosine levels are elevated and some tyrosine is converted into other molecules that may be toxic to cells. It is unclear how impaired break down of tyrosine leads to the skin, eye, and intellectual problems that characterize tyrosinemia type II.

Other Names for This Gene

• ATTY_HUMAN
• L-tyrosine:2-oxoglutarate aminotransferase
• tyrosine transaminase

Genomic Location

Tyrosinemia type II is a genetic condition. Babies inherit it from their biological (birth) parents.

• Tyrosinemia type II is an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking TAT gene to their baby. Only babies with two nonworking TAT genes—one from the mom and one from the dad—have this condition.
  • People with one working copy and one nonworking copy of the TAT gene are called carriers.
  • Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
  • If two parents are carriers of a nonworking copy of the TAT gene, they have a 1 in 4 chance of having a child with tyrosinemia type II.
  • Carriers for tyrosinemia type II often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with tyrosinemia type II.
  • Parents who already have a child with tyrosinemia type II still have a 1 in 4 chance of having another child with tyrosinemia type II. This 1 in 4 chance stays the same for all future children.
• Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it.

Signs of tyrosinemia type II usually begin in the first year of life. These signs may be triggered by eating foods or milk that the body cannot break down or by going long periods without eating. The symptoms can also be caused by illnesses or infections.

Signs of the condition may include the following:

• Increased tear production
• Sensitivity to light (photophobia)
• Eye redness
• Skin lesions on the hands and feet
• Developmental delay

Newborn screening for tyrosinemia type II is done using a small amount of blood collected from your baby’s heel. During screening, a special machine measures how much tyrosine is in your baby’s blood. Babies with high levels of tyrosine might have tyrosinemia type II.

What Happens After an Out-of-Range Screening Result?

If your baby’s blood spot screening result for tyrosinemia type II is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.

An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing.

Your baby may need the following tests after an out-of-range screening result:

• Blood and urine tests
• Genetic testing using a blood sample

You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems in early childhood if they are not diagnosed and treated quickly.

False-positive newborn screening results for this condition can happen. Babies who are born early (premature) may have out-of-range results. Also, babies with an immature liver, liver disease, or jaundice may have false-positive results.

In some cases, babies have temporary high levels of tyrosine that go away over time. This is called transient tyrosinemia of the newborn. It is a harmless condition and is not a lifelong genetic condition like tyrosinemia type I, II, and III.

Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.