Also known as:
- Proline oxidase deficiency
- Pyrroline-5-carboxylate dehydrogenase deficiency
- Pyrroline carboxylate dehydrogenase deficiency
- Prolinemia type I
- Prolinemia type II
Prolinemia (PRO) is an inherited condition in which the body is unable to break down and process certain building blocks of protein, called amino acids. It is considered an amino acid condition because it can lead to high levels of the amino acid, proline, in the body. There are two forms of prolinemia: prolinemia type I (PRO I) and prolinemia type II (PRO II). Both types vary in terms of severity, with some individuals showing no symptoms and others having seizures and/or mild intellectual disability. People with PRO II are more likely to develop symptoms than those with PRO I. Unfortunately, there are no effective treatments for PRO at this time.
Your baby’s doctor may ask you if your baby is showing any of the signs of prolinemia (see Early Signs below).
If your baby’s newborn screening result for prolinemia (PRO) 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.
Follow-up testing will involve checking your baby’s urine and blood samples for signs of prolinemia (PRO). When a child has an amino acid condition, harmful amounts of certain substances build up in the body. Measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has PRO. High levels of the amino acid, proline, in the blood (10-15 times higher than normal) and high levels of a molecule called pyrroline-5-carboxylate in the urine might indicate that your baby has prolinemia type II. Babies with prolinemia type I have high levels of proline in the blood (3-10 times higher than normal) with no presence of pyrroline-5-carboxylate in the urine.
There are two forms of prolinemia, prolinemia type I (PRO I) and prolinemia type II (PRO II). Each form varies with regards to disease severity and symptoms. Many individuals, especially those with PRO I, have no signs or symptoms of the condition.. Signs of a more serious case of prolinemia may include:
- Developmental delay
- Mild intellectual disability
If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
There are currently no treatments available to prevent or delay the signs and symptoms of prolinemia (PRO).
The outcome of prolinemia (PRO) depends on the severity of the condition. Many individuals will not encounter any symptoms of the condition throughout the course of their life. Others will experience seizures or mild intellectual disability, especially those suffering from prolinemia type II (PRO II).
Although there is currently no effective treatment for PRO, some of the associated symptoms (i.e. seizures) tend to disappear in adulthood.
When we eat food, enzymes help break it down. Some enzymes help break down proteins into their building blocks, called amino acids. Other enzymes break down these amino acids into smaller components that can be used by the body. Two specific enzymes known as proline dehydrogenase and pyrroline-5-carboxylate dehydrogenase help the body break down and process the amino acid, proline.
If your baby has prolinemia (PRO), his or her body is missing or making non-working copies of one of these enzymes. In prolinemia type I, the proline dehydrogenase enzyme is not working correctly. In prolinemia type II, the pyrroline-5-caroboxylate dehydrogenase enzyme is not working correctly. Without proper functioning of these enzymes, your baby’s body cannot break down proline. This causes proline and other harmful substances to build up in cells throughout the body, which can result in the signs and symptoms of PRO.
Prolinemia (PRO) is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for the non-functioning enzyme (prolinemia dehydrogenase or pyrroline-5-carboxylate dehydrogenase), 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 prolinemia 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 Prolinemia
Support groups can help connect families who have a child or other family member affected with prolinemia with a supportive community of people who have experience and expertise in living with the condition or with similar metabolic disorders. 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. Some children with prolinemia (PRO) have developmental delays. If you think that your baby is not meeting his or her developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because PRO 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 PRO, 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 National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives 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.
States Screening for Prolinemia
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- Genetics Home Reference: http://ghr.nlm.nih.gov/condition/hyperprolinemia
- On Mendelian Inheritance in Man: http://omim.org/entry/239500
- Office of Rare Disease Research: http://rarediseases.info.nih.gov/GARD/Disease.aspx?diseaseID=2847
- Hiroshi Mitsubuchi, Kimitoshi Nakamura, Shiro Matsumoto, and Fumio Endo. Inborn Errors of Proline Metabolism. J Nutr. 2008 Oct;138(10):2016S-2020S.