FACT SHEET

Dihydropteridine Reductase Deficiency (DHPR deficiency) 

Also known as:

• QDPR Deficiency
• BH4/Tetrahydrobiopterin Deficiency 

 

What is DHPR deficiency?

DHPR deficiency is a neurometabolic disorder caused by a genetic variant in the QDPR (Quinoid Dihydropteridine Reductase) gene. 

The QDPR gene helps make a substance called tetrahydrobiopterin or BH4. 

BH4 is has 2 important functions: 

• It helps break down phenylalanine
• It makes important brain chemicals like dopamine, norepinephrine and serotonin. These are called neurotransmitters. Neurotransmitters help neurons (nerves) communicate with each other and they regulate body functions such as learning, muscle movement, mood and behaviour. 

In DHPR deficiency, there is not enough BH4 available to function. 

 

How is DHPR deficiency caused? 

It is autosomal recessive disorder which means if both parents are carriers of the QDPR gene mutation there is a 25% or 1 in 4 chance that their child will have the disorder. 

 

What happens in DHPR deficiency? 

When DHPR enzyme is deficient, BH4 is not recycled as it should. This reduces the amount of BH4 to process phenylalanine. This will lead to a build-up of phenylalanine causing high blood phenylalanine levels. 

It also causes a reduction in the production of essential neurotransmitters, mainly dopamine and serotonin. However, other neurotransmitters such as epinephrine and norepinephrine are affected too. This leads to low levels of these chemicals in cerebrospinal fluid (CSF) - a fluid that surrounds and protects the brain and spinal cord. 

 

How common is DHPR deficiency? 

• We do not know exactly how many people around the world have BH4-related conditions but they are very uncommon.
• In the UK, about 1 in every 10,000 newborns have high phenylalanine levels when they are tested on newborn screening. 
• BH4 deficiencies make up about 1 to 2% of these cases. 
• DHPR deficiency is the second most common BH4 disorder—about 1 in 3 of BH4 deficiency cases is due to DHPR deficiency.

 

How is DHPR deficiency diagnosed? 

• Babies are tested shortly after birth (newborn screening) to check the levels of phenylalanine in their blood. 
• If phenylalanine is high, doctors first consider a condition called Phenylketonuria (PKU). In rare instances, a BH4 deficiency can be the cause of high blood phenylalanine levels. 
• Consequently, all babies with high phenylalanine levels have extra tests to check for BH4-related problems. This happens when they are first found to have a high blood phenylalanine level following newborn screening. 
• Families should be informed during their first hospital visit with their metabolic team that a BH4 disorder might be possible, even though it may be unlikely. 
• If a BH4 deficiency is suspected, further investigations, such as a lumbar puncture and genetic testing, may be necessary to confirm the diagnosis. 

 

What are the symptoms of DHPR deficiency? 

If DHPR deficiency is not detected in newborn screening, symptoms will usually appear within the first six months of life.

Symptoms may include:

• Low birth weight
• Restricted head growth 
• Seizures
• Unusual movements in the arms and legs
• Delays in development and learning 
• Rapid mood changes or emotional ups and downs
• Speech that’s slow to develop
• Excessive sweating or drooling
• Difficulty with feeding or swallowing

 

Who is involved in the care of DHPR deficiency?

Managing DHPR deficiency requires a multidisciplinary team working together to support a child’s development and wellbeing. The hospital team consist of: 

• A neurologist and metabolic doctor - these specialist doctors monitor brain development, movement, and development. They also guide treatment plans to manage phenylalanine levels and help replace the neurotransmitters that are not being made by the body.  
• Specialist nurse – will help coordinate care, monitors progress, and offers practical support to families
• Dietitian – guides the low phenylalanine diet and helps with food choices, daily protein exchanges, and monitors overall nutrition.
• Specialist therapists - this could include physiotherapists, occupational therapists and speech and language therapists. 

 

How is DHPR deficiency treated? 

Early diagnosis is important as early treatment can lead to good outcomes. However, even with early treatment, children can develop challenges with learning and movement.

The following treatment is given: 

• A low phenylalanine diet: this helps reduce phenylalanine in the blood. Sometimes a medicine called sapropterin is used to make the diet more relaxed and allow more protein.   
• Medicines to replace brain chemicals (neurotransmitters). Since the brain cannot  make enough dopamine, norepinephrine or serotonin, doctors prescribe regular L-dopa and 5-hydroxytryptophan (5-HTP) to replace these. These medications may have side-effects. 
• Folinic acid supplements to support levels of folate in the brain. 
• Other medicines: Specialist centres may suggest other medicines depending on a  child’s needs.

 

DHPR deficiency and PKU: How are they connected?

DHPR deficiency is not the same as Phenylketonuria (PKU), but there are some important similarities:

• Both conditions require a low phenylalanine diet to protect the brain.
• Regular blood tests are needed to check blood phenylalanine levels.
• Daily protein exchanges are calculated in the same way for both conditions. 

Even though DHPR deficiency is different, families often use the same low protein diet resources and approaches familiar to the PKU community.

Please do get in touch if you or someone you know has been affected by DHPR Deficiency.