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thiopurine S-methyltransferase deficiency (TPMT deficiency)
Genetics:
- associated with defects in thiopurine S-methyltransferase (TPMT)
- TPMT deficiency inherited by TPMT*2 & TPMT*3A alleles, are the most prevalent mutant TPMT in humans
- TPMT deficiency is associated with lower cellular levels of TPMT protein & the protein encoded by TPMT*2 & TPMT*3A mutant alleles are degradated more rapidely by an ATP-dependent proteasome-mediated pathway
Pharmacology:
- disruption of normal metabolic inactivation of thiopurine drugs
- patients with intermediate or no TPMT activity are at risk of toxicity after receiving standard doses of thiopurine drugs
- inter-individual differences in response to these drugs are largely determined by genetic variation at the TPMT locus
- patients with TPMT deficiency should receive significantly lower doses of thiopurines (i.e. azathioprine) than other patients
General
enzyme deficiency
Database Correlations
OMIM 610460
References
OMIM :accession 610460