Conditions Pyroglutamic Acidemia
Pyroglutamic acidemia (5-OXO) is an inherited condition in which the body is unable to properly produce glutathione. This is problematic because the body needs glutathione to protect cells in the course of energy production, process and remove medications and cancer-causing compounds, and build DNA. There are three types of 5-OXO that differ in severity. All forms of 5-OXO usually result in the destruction of red blood cells (hemolytic anemia), which can cause chills, tiredness, rapid heart rate and other symptoms. Individuals with the severe form may also develop frequent bacterial infections and neurological symptoms including seizures, slowing down of physical reactions, movements, speech, intellectual disabilities, and a loss of coordination. For the best possible outcome, it is important to identify 5-OXO through newborn screening and begin proper treatment early.
5-OXO is very rare. It has only been documented in 70 people worldwide.
Also known as
- Glutathione synthetase deficiency
- Deficiency of glutathione synthase
- Pyroglutamic acidemia
- Pyroglutamic aciduria
Your baby’s doctor may ask you if your baby is showing any of the signs of 5-OXO (see Early Signs below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for pyroglutamic acidemia (5-OXO) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your child to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated 5-OXO can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s urine and blood samples for signs of 5-OXO. Sometime, your baby’s doctor may need to evaluate a small sample of skin, as well. When a child has 5-OXO, they may have elevated or reduced levels of certain substance in the body. High amounts of 5-oxoproline in the urine or low levels of glutathione synthetase (GSS) in blood or skin cells might indicate that your baby has 5-OXO.
About Pyroglutamic Acidemia
Signs of pyroglutamic acidemia (5-OXO) can begin any time from infancy to adulthood and have a variety of severity. Usually, signs can begin as early as a couple days after birth. Signs of 5-OXO include:
- Delayed growth
- Developmental delays
- Intellectual Delays
- Pale Skin Color
- Yellow Skin Color (Jaundice)
- Poor appetite
- Sleeping longer or more often
- Breathing trouble
- Trouble regulating body temperature (your baby might get cold easily)
If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Supplements and Medications
Your baby’s health care provider may prescribe medications and supplemental vitamins C and E to help your baby’s body maintain a healthy red blood cell count and prevent the buildup of harmful acids.
Pyroglutamic academia is a very rare condition so there are little data available regarding the long-term outcome. However, there is evidence that children who are treated early for 5-OXO can have healthy growth and development. This is why newborn screening for 5-OXO is so important.
Even with treatment, some children may experience learning disabilities, intellectual disabilities, or neurological affects, which are commonly associated with 5-OXO.
Children who do not receive treatment for 5-OXO are at risk for seizures, brain damage, or coma.
Children with pyroglutamic acidemia (5-OXO) have low levels of a substance called glutathione synthetase which helps the body make an important molecule called glutathione. The body needs glutathione to protect cells from damage in the course of energy production, process and remove medications and cancer-causing compounds, and build essential cellular components such as DNA and proteins. Without proper amounts of glutathione, the body is unable to perform these functions, leading to the symptoms of 5-OXO.5-OXO is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for 5-OXO, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with 5-OXO is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Pyroglutamic Acidemia
Support groups can help connect families who have a child or other family member affected with 5-OXO with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.
Work with your baby’s health care provider to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a physician that specializes in metabolism and other medical resources in your community. Some children with 5-OXO have developmental delays. If you think that your baby is not meeting their developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because 5-OXO is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for 5-OXO, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the American College of Medical Genetics and Genomics (ACMG) and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.
References & Sources
Visit OMIM to search its online catalog of human genes and disorders
Visit MedlinePlus Genetics for more condition information
Visit OrphaNet for more information on glutathione synthetase deficiency
For more information on inborn errors in the metabolism of glutathione, visit the Orphanet Journal of Rare Diseases
Simon E, Vogel M, Fingerhut R, et al. Diagnosis of glutathione synthetase deficiency in newborn screening. J Inherit Metab Dis. 2009;32 Suppl 1:S269-72.