General Condition Information
- Pyroglutamic acidemia
- It is unknown how many babies are born with this rare condition each year in the United States.
What is Glutathione Synthetase Deficiency
Glutathione synthetase deficiency is an inherited (genetic) condition that prevents the production of a substance called glutathione. Glutathione is an antioxidant that helps protect the body from toxic substances.
Glutathione synthetase is an enzyme that helps make glutathione. Glutathione protects cells from damage by neutralizing harmful substances. Glutathione supports breaking down a substance called 5-oxoproline.
There are three types of glutathione synthetase deficiency – mild, moderate, and severe – and they differ in signs, symptoms, and age of onset.
Low levels of glutathione and high levels of 5-oxoproline can damage your baby’s body. If untreated, this damage leads to the signs and symptoms of the condition.
Newborn Screening and Follow-Up
Newborn screening for glutathione synthetase deficiency requires collecting a small amount of blood from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
Screening measures how much 5-oxoproline is in your baby’s blood. Babies with high levels of 5-oxoproline might have glutathione synthetase deficiency.
If your baby’s blood spot screening result for glutathione synthetase deficiency 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. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or 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 soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition can happen.
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.
Signs of glutathione synthetase deficiency are typically present shortly after birth. In some cases, signs and symptoms show up later in infancy.
Signs of the condition may include the following:
The condition is caused by a change in the GSS gene. This gene gives the body instructions for making glutathione synthetase, the enzyme that helps make glutathione.
Without a working GSS gene, your baby’s body cannot make enough working glutathione synthetase enzyme. As a result, their body has trouble making glutathione.
If glutathione is not made, harmful levels of 5-oxoproline build up in your baby’s body and your body cannot protect itself as well from toxic substances.
- Glutathione synthetase deficiency is an autosomal recessive condition. Babies inherit it when each parent passes down a nonworking GSS gene to their baby. Only babies with two nonworking GSS genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the GSS 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 GSS gene, they have a 1 in 4 chance of having a child with glutathione synthetase deficiency.
- Carriers for glutathione synthetase deficiency 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 glutathione synthetase deficiency.
- Parents who already have a child with glutathione synthetase deficiency still have a 1 in 4 chance of having another child with glutathione synthetase deficiency. This 1 in 4 chance stays the same for future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Medications to get rid of extra acid in the body
- Vitamin supplements
Children who receive early and ongoing treatment for glutathione synthetase deficiency can have healthy growth and development.