Dihydropyrimidinase Deficiency

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This disorder is caused by a problem with the DPYS gene. This gene provides instructions for making an enzyme called dihydropyrimidinase which helps break down molecules that constitute the core of DNA and RNA. We call them pyrimidines.

If you have a problem in the DPYS gene, you will not produce enough or any of the dihydropyrimidinase enzyme at all. Therefore, you will be unable to break down pyrimidines that in turn build up in the blood and in the fluid that protects the brain and the spinal cord. Consequently, it is released in the urine. The inability to break down pyrimidines also disrupts other following processes whose role is to protect the nervous system and help it function properly. This causes neurological problems in some of the affected individuals.

We do not know how many people have this disorder. It is very rare with only a small amount of cases that are known. Due to its rarity, it is also unknown whether it affects more males or females or any specific ethnicity.

Signs and symptoms usually start to appear during infancy or childhood and vary greatly in severity from mild to severe manifestations. In fact, some affected individuals can live asymptomatic life and are only diagnosed by laboratory testing.  

 Neurological signs and symptoms include:  

 Intellectual disability 

• Seizures 
• Weak muscle tone (hypotonia) 
• Abnormally small head size (microcephaly) 
• Dysmorphic features 
• Autistic behaviours that affect communication and social interaction 

Gastrointestinal signs and symptoms usually include: 

• Backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) 
• Recurrent episodes of vomiting (cyclic vomiting) 
• Deterioration of the small, finger-like projections that line the small intestine and provide a large surface area with which to absorb nutrients (villous atrophy) 
• Difficulty absorbing nutrients from foods (malabsorption) 
• Failure to grow and gain weight at the expected rate (failure to thrive) 

Affected individuals, including those without any signs and symptoms, tend to be vulnerable to drugs called fluoropyrimidines that are used to treat cancer. This drug may induce a severe, potentially life-threatening toxic reaction, that includes gastrointestinal problems, and blood abnormalities among other problems. 

You will be diagnosed after a clinical examination by your specialist or doctor. However, as the signs and symptoms of this disorder are similar to other conditions, you will need further tests. Doctors will conduct specialised laboratory blood tests. Other tests may include a DNA test or a specialised procedure called a liver biopsy.  

Unfortunately, there is no cure for Dihydropyrimidinase deficiency. The treatment is focused on managing individual symptoms and providing comfort and relief in the form of supporting the individual and any family members. A multi-disciplinary team of specialists and support networks will be involved in the management of the condition and to offer practical and emotional support. 

Dihydropyrimidinase deficiency can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier. 

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have. 

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.  

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited Dihydropyrimidinase deficiency. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own. 

References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: AAP002].