Purine nucleoside phosphorylase deficiency

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Purine nucleoside phosphorylase deficiency [PNP deficiency] is an autosomal recessive condition. It is believed that this condition is caused by a mutation in the PNP gene. This gene provides instructions for the body to produce the enzyme, purine nucleoside phosphorylase. This enzyme is found mostly in white blood cells and is involved in clearing away waste molecules that have been producing whilst making DNA. Without this enzyme or only having it in limited quantities, this can lead to a build-up of a harmful substance called deoxyguanosine triphosphate (dGTP). This molecule can damage immature cells and ultimately cause them to self-destruct.

Those diagnosed with PNP deficiency tend to have a low number of T cells circulating in their blood. These cells are known to protect the immune system against invading bacteria. Individuals may also have low B cells; these cells usually mature into plasma cells and produce antibodies which also help to stop pathogens invading the body. A lack of these immune cells can lead to serious health complications due to frequent infections. Opportunist organisms may seek out to damage the cells in your body, pathogens that would usually not do any harm but due to your immune system being compromised, they can be quite serious. If the condition is left untreated, the consequences may be fatal within the first 2 decades of life.

Currently, It is estimated that 70 people worldwide have been diagnosed with this condition. Due to the rarity of this condition it is unclear if PNP deficiency presents more in females or males or is more prominent with specific ethnicities.

As explained above, this condition can leave your immune system compromised. First signs and symptoms are presented in infancy or childhood. Some of the other signs and symptoms of this condition are:

• Repeat infections which can be serious
• Delayed growth
• Muscle stiffness
• Difficulty with balance and coordination
• Damage to brain cells
• Neurological problems
• Intellectual difficulties
• Haemolytic anaemia

People diagnosed with this condition are at increased risk of a variety of autoimmune conditions. This will be explained on diagnosis by your health care professional.

Diagnosis for this condition is usually made by blood sample analysis for immune cells and increased urine or blood levels of inosine, guanosine and their deoxy forms. Displaying physical symptoms of this condition alongside findings in blood samples and genetic testing improves the accuracy of diagnosis.

A bone marrow transplant to produce stem cells which can mature into T cells and B cells is one method for the severe form of this condition. This is a treatment that involves 5 main stages and in summary transfers new stem cells into your body through something called a central line. This treatment is usually done under general anaesthesia. Although this treatment has not shown to be beneficial with neurological systems experienced with this condition. The frequent use of blood transfusions has been shown to provide a temporary benefit to the user.

PNP 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 PNP 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.

If you have previously had a child with PNP deficiency and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.

References are available on request. Please contact us on 0800 652 3181 or by emailing contact@metabolicsupport.org.

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.