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

More general terms

• enzyme deficiency

Database

• OMIM: https://mirror.omim.org/entry/610460