National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Thiopurine S methyltranferase deficiency


Other Names:
TPMT deficiency; Thiopurines, poor metabolism of; Thiopurine methyltransferase deficiency; TPMT deficiency; Thiopurines, poor metabolism of; Thiopurine methyltransferase deficiency; 6-mercaptopurine sensitivity See More
Categories:
Thiopurine S-methyltransferase deficiency is an autosomal recessive disorder that affects the body's ability to metabolize thiopurine drugs. Thiopurine S-methyltransferase (TPMT) is an enzyme that the body uses to break down thiopurine drugs. Thiopurine S-methyltransferase deficiency patients have a mutation in either one or both copies of the TPMT gene that causes reduced enzyme activity and difficulties breaking down thiopurine drugs. Affected individuals are at a high risk of experiencing bone marrow damage if they take thiopurine drugs. Many patients recover from the bone marrow damage once thiopurine drug use is stopped. However when the bone marrow is damaged, infections can cause serious health problems and may be life-threatening. To reduce the risk of bone marrow damage, thiopurine therapy should be lowered based on how many mutations a patient has in the TPMT gene. [1]
Last updated: 8/29/2012

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Abnormality of blood and blood-forming tissues 0001871
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Autosomal recessive inheritance 0000007
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Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.
The National Institutes of Health Clinical Pharmacogenomics Implementation Consortium isssued recommendations on how to manage patients with TPMT deficiency. They recommend that patients with one TPMT gene change reduce thiopurine doses by about 30-70%. Patients with two TPMT gene changes should reduce thiopurine doses by at least 10-fold. The frequency of doses should also be reduced from daily to three times per week.[2]
Last updated: 8/29/2012

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Thiopurine S methyltranferase deficiency. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Thiopurine S methyltranferase deficiency. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My daughter has been diagnosed with this condition and her doctors do not know how to treat her. They do not understand that she cannot be exposed to toxins of any kind. How should she be treated? See answer


  1. Barlow N. Thiopurine S-methyltransferase deficiency. Orphanet. May 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=3315. Accessed 8/29/2012.
  2. Relling MV, Gardner EE, Sandborn WJ et al. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. March 2011; 3:387-391. http://www.ncbi.nlm.nih.gov/pubmed/21270794. Accessed 8/29/2012.