thiopurine S-methyltransferase deficiency

Thiopurine S-Methyltransferase (TPMT) Deficiency: A Condition Characterized by Reduced Drug Metabolism

Thiopurine S-methyltransferase (TPMT) deficiency is a condition where the body's ability to process certain drugs, known as thiopurines, is significantly impaired. Thiopurines are a class of medications used to treat various conditions, including autoimmune diseases, cancer, and inflammatory bowel disease.

Key Features of TPMT Deficiency

• Reduced activity of the TPMT enzyme, which leads to inadequate metabolism of thiopurine drugs [1]
• Increased risk of adverse reactions to thiopurines due to accumulation of these medications in the body [7]
• Potential for life-threatening complications, such as pancytopenia (a condition characterized by a reduction in all blood cell types) [7]

Causes and Prevalence

TPMT deficiency is an autosomal codominant inherited metabolic condition, caused by mutations to the TPMT gene. It is estimated that approximately 1 in 300 individuals are homozygous for deleterious mutations, making them susceptible to TPMT deficiency [8].

Implications and Management

Individuals with TPMT deficiency require careful consideration of thiopurine therapy, as standard doses can be toxic. A personalized approach to dosing is essential to minimize the risk of adverse reactions while still achieving therapeutic benefits.

References: [1] Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process drugs... [Context 1] [7] Thiopurine S-methyltransferase (TPMT) deficient patients develop life-threatening haematotoxicity (for example, pancytopenia) when treated with a standard... [Context 7] [8] TPMT deficiency is an autosomal recessive condition with an incidence of approximately 1 in 300 individuals homozygous for deleterious mutations... [Context 8]

Thiopurine S-methyltransferase (TPMT) deficiency is a genetic condition that affects the body's ability to metabolize certain medications, including thiopurines. Individuals with TPMT deficiency may experience various signs and symptoms, which can range from mild to severe.

Some of the common signs and symptoms of TPMT deficiency include:

• Abnormality of blood-forming tissues
• Anaemia (a condition characterized by a lack of red blood cells or hemoglobin)
• Abnormality of metabolism

These symptoms can occur due to the body's inability to effectively metabolize thiopurines, leading to an accumulation of toxic substances in the body. In severe cases, TPMT deficiency can lead to life-threatening complications.

It is essential for individuals with TPMT deficiency to work closely with their healthcare providers to manage their condition and prevent potential complications. Regular monitoring and adjustments to medication regimens can help minimize the risk of adverse effects.

References: * [2] Some of the signs and symptoms of Thiopurine S-methyltransferase deficiency are: Abnormality of blood forming tissues; Anaemia; Abnormality of metabolism. * [6] Homozygous polymorphisms associated with absence of thiopurine methyltransferase (TPMT) can cause life-threatening azathioprine-induced myelotoxicity.

Understanding Thiopurine S-Methyltransferase (TPMT) Deficiency

Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of the enzyme TPMT, which helps the body process certain medications. This deficiency can lead to excessive myelosuppression or severe hematopoietic toxicity in individuals who take thiopurine drugs.

Diagnostic Tests for TPMT Deficiency

Several diagnostic tests are available to detect TPMT deficiency:

• TPMT activity test (phenotype): This method tests the activity level of the enzyme TPMT in a person's red blood cells. It is a useful tool for identifying individuals with low or intermediate TPMT activity who may be at risk for myelosuppression when taking thiopurine medications [6][9].
• Genetic testing: Genetic testing can detect mutations in the TPMT gene that are associated with TPMT deficiency. This type of testing is often used to confirm a diagnosis and provide information on the genetic basis of the condition [4][7].

Other Relevant Information

• Thiopurine S-methyltransferase (TPMT) activity test requires physician attestation that patient consent has been received if ordering medical facility is located in AK, DE, FL, GA, MT, ND, OR, SD, and UT [2].
• TPMT deficiency can be detected using a germline genetic test, which requires physician attestation for certain locations [2].

References

[1] TPMT activity test (phenotype) - This method tests the activity level of the enzyme thiopurine S-methyltransferase (TPMT) in a person's red blood cells. [4] by CR Yates · 1997 · Cited by 989 — The detection of TPMT mutations provides a molecular diagnostic method for prospectively identifying TPMT-deficient and heterozygous patients. Publication types. [6] TPMT activity test (phenotype)—this method tests the activity level of the enzyme thiopurine S-methyltransferase (TPMT) in a person’s red blood cells. [7] Feb 22, 2024 — This Test Fact Sheet focuses on genetic testing for TPMT and NUDT15 variants, which can be performed prior to or during thiopurine therapy. The ... [9] This assay is used to detect individuals with low and intermediate thiopurine methyltransferase (TPMT) activity who may be at risk for myelosuppression when ...

Treatment Options for Thiopurine S-Methyltransferase (TPMT) Deficiency

Thiopurine S-methyltransferase (TPMT) deficiency is a condition that affects the metabolism of certain medications, including azathioprine, 6-mercaptopurine, and thioguanine. These drugs are commonly used to treat autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and prevent rejection in transplant patients.

Safe Treatment Options

Research has shown that TPMT deficient patients can be safely treated with alternative dosing regimens of azathioprine (AZA) [1]. In fact, a study published in 2003 reported for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA [4].

Alternative Medications

In addition to adjusting the dosage of azathioprine, other medications can be used as alternatives. For example, allopurinol has been shown to be a safe and effective treatment option for TPMT deficient patients [9]. Allopurinol is a xanthine oxidase inhibitor that can help reduce the toxicity associated with thiopurine therapy.

Immunosuppressive Agents

Thiopurines like azathioprine, 6-mercaptopurine, and thioguanine are efficient immunosuppressive agents for the management of autoimmune diseases [8]. However, in TPMT deficient patients, these medications can be toxic at standard doses.

Conclusion

In conclusion, while TPMT deficiency presents a challenge to treating certain medical conditions, there are safe treatment options available. Alternative dosing regimens and medications like allopurinol can help mitigate the toxicity associated with thiopurine therapy.

References:

[1] by BA Kaskas · 2003 · Cited by 197 — We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. [2] Apr 1, 2015 — These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. [3] These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body's immune system. [4] by BA Kaskas · 2003 · Cited by 197 — We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. [5] Nov 9, 2021 — Examples of thiopurines include azathioprine, mercaptopurine, and thioguanine. These medications are used to treat diseases such as acute ... [6] Feb 22, 2024 — Thiopurine drug therapy is used to treat autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection ... [7] Thiopurine methyltransferase (TPMT) deficiency is a condition in which patients treated with standard doses of azathioprine (AZA, Imuran), 6-mercaptopurine (6- ... [8] Thiopurines like azathioprine [AZA], 6-mercaptopurine [6-MP] and thioguanine are efficient immunosuppressive and cytotoxic agents for the management of ... [9] Recent evidence suggests that TPMT is inducible by mesalamine, a common concomitant drug used in the treatment of inflammatory bowel disease, with potential for ... [10] by B Warner · 2018 · Cited by 89 — Allopurinol is a safe drug with the main side ... Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine.

Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process certain medications, such as azathioprine and mercaptopurine. Differential diagnosis of TPMT deficiency involves identifying other conditions that may present with similar symptoms.

Conditions to Consider:

• Other genetic disorders: Conditions like glucose-6-phosphate dehydrogenase (G6PD) deficiency or other enzymatic deficiencies can cause similar symptoms.
• Medication side effects: Other medications, such as certain antibiotics or anticonvulsants, can also cause myelosuppression or other adverse reactions.
• Inflammatory bowel disease (IBD): Patients with IBD may experience similar symptoms due to the underlying condition itself.

Diagnostic Approach:

1. Medical history and physical examination: A thorough medical history and physical examination are essential in identifying potential causes of TPMT deficiency.
2. Laboratory tests: Blood tests, such as complete blood counts (CBC) and liver function tests, can help identify other conditions that may be causing the symptoms.
3. Genetic testing: Genetic testing for TPMT deficiency is a crucial step in diagnosing this condition.

Key Points to Consider:

• TPMT deficiency is a rare genetic disorder that affects the body's ability to process certain medications.
• Differential diagnosis of TPMT deficiency involves considering other conditions that may present with similar symptoms.
• A thorough medical history, physical examination, and laboratory tests are essential in identifying potential causes of TPMT deficiency.

References:

[1] Thiopurine S-methyltransferase (TPMT) deficiency is a condition characterized by significantly reduced activity of an enzyme that helps the body process certain medications. [1] [3] Thiopurine S-methyltransferase polymorphisms have been linked with severe and potentially fatal myelosuppression in deficient individuals. [3] [8] Thiopurine methyltransferase (TPMT), the first identified variant impacting IBD therapy, is involved in thiopurine metabolism with decreased activity resulting in adverse reactions. [8] [9] Defective TPMT causes TPMT deficiency, which can lead to severe and potentially fatal myelosuppression. [9]

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