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

• DHPR Deficiency Disorder
• Phenylketonuria Type 2
• Quinoid Dihydropteridine Reductase Deficiency Disorder

What is Dihydropteridine Reductase Deficiency Disorder? (Definition/Background Information)

• Dihydropteridine Reductase Deficiency Disorder (DHPR Deficiency Disorder) is a severe form of hyperphenylalaninemia (high levels of the amino acid phenylalanine in the blood) due to impaired renewal of a substance known as tetrahydrobiopterin (BH4)
• Tetrahydrobiopterin normally helps process several amino acids, including phenylalanine, and it is also involved in the production of neurotransmitters. If little or no tetrahydrobiopterin is available to help process phenylalanine, this amino acid can build up in the blood and other tissues and the levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid are also decreased
• This results in neurological symptoms such as psychomotor delay, low muscle tone (hypotonia), seizures, abnormal movements, too much salivation, and swallowing difficulties
• DHPR Deficiency Disorder is caused by mutations in the QDPR gene. It is inherited in an autosomal recessive manner
• The treatment of Dihydropteridine Reductase Deficiency Disorder should be started as soon as possible and includes BH4 supplementation usually combined with a diet without phenylalanine, folate supplementation, and specific medications to restore the levels of neurotransmitters in the brain

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

Who gets Dihydropteridine Reductase Deficiency Disorder? (Age and Sex Distribution)

• Dihydropteridine Reductase Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur soon after birth or in infancy
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected. However, the condition is more common in countries near the Mediterranean sea

What are the Risk Factors for Dihydropteridine Reductase Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Dihydropteridine Reductase Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this deficiency 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 Dihydropteridine Reductase Deficiency Disorder? (Etiology)

• Dihydropteridine Reductase Deficiency Disorder is caused by mutations in the QDPR gene
• It is inherited in an autosomal recessive manner

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

Autosomal recessive inheritance: 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 Dihydropteridine Reductase Deficiency Disorder?

The signs and symptoms of Dihydropteridine Reductase Deficiency Disorder may include:

• Cerebral calcification
• Choreoathetosis
• Episodic fever
• Excessive salivation
• Global developmental delay
• Hyperphenylalaninemia
• Hypertonia
• Irritability
• Muscular hypotonia
• Myoclonus
• Progressive neurologic deterioration
• Tremor

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

How is Dihydropteridine Reductase Deficiency Disorder Diagnosed?

Dihydropteridine Reductase Deficiency Disorder 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 QPDR gene mutation(s)

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 Dihydropteridine Reductase Deficiency Disorder?

The complications of Dihydropteridine Reductase Deficiency Disorder may include:

• Severe developmental delay
• Problems with brain function due to abnormalities in levels of crucial neurotransmitters, which may lead to behavioral issues

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

How is Dihydropteridine Reductase Deficiency Disorder Treated?

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

The treatment may include:

• BH4 supplementation 
• Folate supplementation
• A diet without phenylalaninefolate 
• Specific medications to restore the levels of neurotransmitters in the brain

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

How can Dihydropteridine Reductase Deficiency Disorder be Prevented?

Dihydropteridine Reductase Deficiency Disorder 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), if available, 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 Dihydropteridine Reductase Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Dihydropteridine Reductase Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any
• Without prompt treatment, the affected individuals may succumb to the condition during infancy or in childhood

Additional and Relevant Useful Information for Dihydropteridine Reductase Deficiency Disorder:

Dihydropteridine Reductase Deficiency is also known by the following names:

• BH-4-Deficient Hyperphenylalaninemia
• Hyperphenylalaninemia due to Dihydropteridine Reductase Deficiency
• PKU Type 2
• QDPR Deficiency Disorder

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

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