Thiopurine S-methyltransferase deficiency

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Thiopurine S-methyltransferase deficiency is an autosomal codominant inherited metabolic condition which is believed to be caused by mutations to the MPT gene. This gene mutation results in the decline of the TMPT enzymes which is useful for processing a brand of drugs called thiopurines. There are three enzymes which can metabolise these drugs, these are azathioprine, mercaptopurine, and thioguanine. Thiopurines are used to inhibit the body’s immune system when necessary. Inhibition of the immune system would be necessary to treat conditions such as, Crohns disease and arthritis which are caused by malfunctions to your immune system. Thiopurines are also used in line with treating leukaemia’s, cancers of the immune system cells and are commonly used in organ transplants.

Thiopurines are commonly used to inhibit the actions of immune system and prevent it from recognising the transplant cells or organ as non self or as an infection. With this condition, Thiopurines are broken down by the mutated enzyme TMPT and turn the drug into the inactive form so it cannot inhibit the immune system. If this is left unchecked, then the body can continue to destroy immune cells which can lead to potential life threatening health complications.

Current research suggests that Thiopurine S-methyltransferase deficiency impacts up to 1 percent of the worldwide population. A further 11 percent have been shown to have depleted levels of the enzyme which is associated with this condition.

The signs and symptoms of this condition can be quite varied, and they can be particular to the individual who has been diagnosed. The age at which this condition presents is currently unclear due to the rarity of the condition and the number of people who have been diagnosed with this condition. Some of the signs and symptoms of Thiopurine S-methyltransferase deficiency are:

• Abnormality of blood forming tissues
• Anaemia
• Abnormality of metabolism

Alongside displaying the physical features of this condition, Thiopurine S-methyltransferase deficiency can commonly be diagnosed by a blood test. As diagnosis is made by analysing  red blood cells, if you have recently had a blood transfusion the recorded amount would be inaccurate.

It has been recommended for individuals who have been diagnosed with this condition to reduce their thiopurine dose by 30-70% in order to not experience the symptoms that are commonly expected with Thiopurine S-methyltransferase deficiency. It is also suggested that individuals with this condition reduce their intake of this drug from daily dosage to 3 times per week.

Thiopurine S-methyltransferase deficiency can only be passed on to a child if both parents has one of the two copies of the faulty gene, this is referred to as autosomal codominance. Autosomal codominant inheritance is defined by the ability to detect either or both of two alleles in an individual that cause the genetic condition.

 Once you are diagnosed, you can speak to a genetic counsellor for more information. They can explain how you may have inherited Thiopurine S-methyltransferase 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 Thiopurine S-methyltransferase 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.

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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.