Hyperprolinemia is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the proteins you eat into amino acids. The amino acids then become part of other proteins you need to function.

There are enzymes that break down an amino acid called proline. The process of breaking down proline happens in steps. Each step needs a specific enzyme. There are two types of hyperprolinemia: type I and type II, depending on which enzyme in the process is not working.

In hyperprolinemia type I, the enzyme needed for the first step, proline oxidase, is not working well. In hyperprolinemia type II, the enzyme needed for the second step, pyrroline-5-carboxylate dehydrogenase, is not working. In both types of hyperprolinemia, the body does not make enough enzyme or does not make the enzyme correctly. People with hyperprolinemia have trouble breaking down proline.

A buildup of proline can damage the brain. Without treatment, this damage can lead to the signs and symptoms of the condition.

A change in the ALDH4A1 and PRODH genes causes this condition. The PRODH gene causes hyperprolinemia type I. The ALDH4A1 gene causes hyperprolinemia type II. These genes give the body instructions for making enzymes that break down proline (proline oxidase and pyrroline-5-carboxylate dehydrogenase).

Without a working ALDH4A1 or PRODH gene, the body cannot break down enough proline. As a result, proline and related substances can build up and, in some cases, cause damage to the body.

Hyperprolinemia is a genetic condition. Babies inherit it from their biological (birth) parents.

• Hyperprolinemia is an autosomal recessive condition. Babies inherit the condition when each parent passes down the same nonworking gene that causes hyperprolinemia (PRODH or ALDH4A1) to their baby. Only babies with two matching nonworking genes—for example, one nonworking PRODH from the mom and one nonworking PRODH from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking PRODH from the mom and one nonworking ALDH4A1 from the dad—will not have this condition.
  • People with one working copy and one nonworking copy of the ALDH4A1 or PRODH 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 ALDH4A1 or PRODH gene, they have a 1 in 4 chance of having a child with hyperprolinemia.
  • Carriers for hyperprolinemia 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 hyperprolinemia.
  • Parents who already have a child with hyperprolinemia still have a 1 in 4 chance of having another child with hyperprolinemia. 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.

Most babies with hyperprolinemia type I will have no signs or symptoms. People with hyperprolinemia type II are more likely to have some signs or symptoms of the condition.

In the very rare cases where a person does have signs or symptoms, these may include the following:

• Seizures
• Development delay
• Mild intellectual disability

Newborn screening for hyperprolinemia requires collecting a small amount of blood from your baby’s heel. Screening measures how much proline is in your baby’s blood. Babies with high levels of proline might have hyperprolinemia.

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

If your baby’s blood spot screening result for hyperprolinemia 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 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.

Babies and children with hyperprolinemia typically do not need any treatment. If your baby does have signs and symptoms of hyperprolinemia, it is important to talk to your health care provider about which treatment(s), if any, your baby needs.