What are the other Names for this Condition? (Also known as/Synonyms)

• Proline Hydrogenase Deficiency Disorder
• Proline Oxidase Deficiency Disorder

What is Hyperprolinemia? (Definition/Background Information)

• Hyperprolinemia is when there is an excess of a particular protein building block (amino acid), called proline, in the blood
• This condition generally occurs when proline is not broken down properly by the body
• There are two inherited forms:
  • Hyperprolinemia type 1
  • Hyperprolinemia type 2
• People with Hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level
• Less commonly, affected individuals can experience seizures, intellectual disability, or other neurological or psychiatric problems
• Hyperprolinemia is caused by mutations in the PRODH gene and is inherited in an autosomal recessive pattern

(Source: Hyperprolinemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Individuals with Hyperprolinemia type 2 exhibit 10-15 fold higher than normal levels of proline in their blood, as well as elevated levels of a related compound known as pyrroline-5-carboxylate
• Such individuals are more likely to be affected by seizures or intellectual disability

Who gets Hyperprolinemia? (Age and Sex Distribution)

• Hyperprolinemia is a rare congenital disorder. The exact prevalence of this condition is not known
• The presentation of symptoms may occur at any age
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hyperprolinemia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hyperprolinemia can be inherited
• Currently, no other risk factors have been clearly identified for the disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hyperprolinemia? (Etiology)

• Hyperprolinemia type 1 is caused by mutation(s) in the PRODH gene, and the type 2 disease is caused by ALDH4A1 gene mutations
• Causative mutations in either gene are inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Hyperprolinemia?

The signs and symptoms of Hyperprolinemia may differ in type and severity among affected individuals, and may include:

• Aggressive behavior
• EEG abnormality
• Generalized hypotonia
• Global developmental delay
• Hydroxyprolinuria
• Hyperactivity
• Hyperglycinuria
• Hyperprolinemia
• Nephropathy
• Prolinuria
• Proteinuria
• Schizophrenia
• Status epilepticus
• Stereotypy

(Source: Hyperprolinemia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hyperprolinemia Diagnosed?

Hyperprolinemia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutations

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hyperprolinemia?

The complications of Hyperprolinemia may include:

• Risk of falls and injury due to seizures
• Severe behavioral problems
• Progressive deterioration of speech and motor functions
• Severe intellectual deficiency

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hyperprolinemia Treated?

There is no cure for Hyperprolinemia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Hyperprolinemia be Prevented?

Currently, Hyperprolinemia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hyperprolinemia? (Outcomes/Resolutions)

• The prognosis of Hyperprolinemia is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hyperprolinemia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/