Thiopurine S-methyltransferase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: TPMT DEFICIENCY
THIOPURINES, POOR METABOLISM OF
Number of Symptoms 8
OrphanetNr: 3315
OMIM Id: 610460
ICD-10: E79.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of purine metabolism
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
(HPO:0001871) Abnormality of blood and blood-forming tissues 37 / 7739
2
(HPO:0001939) Abnormality of metabolism/homeostasis 328 / 7739
3
(OMIM) Increased toxic thioguanine nucleotides (TGNs) on standard doses of thiopurine drugs 1 / 7739
4
(OMIM) Myelosuppression develops on standard doses of thiopurine drugs 1 / 7739
5
(HPO:0000007) Autosomal recessive inheritance 2538 / 7739
6
(OMIM) Decreased metabolism of thiopurine drugs 1 / 7739
7
(OMIM) Decreased activity of thiopurine S-methyltransferase 1 / 7739
8
(OMIM) Hematopoietic toxicity develops on standard doses of thiopurine drugs 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) TPMT deficiency is an autosomal recessive trait associated with severe hematopoietic toxicity when patients are treated with standard doses of the antineoplastic agents 6-mercaptopurine (6MP) or 6-thioguanine (6TG), or the immunosuppressant azathioprine (AZA) (Lennard et al., 1989). ...
Clinical Description OMIM Lennard et al. (1987, 1990) found a significant negative correlation between erythrocyte cytotoxic TGNs and TPMT activity among children with acute lymphoblastic leukemia (ALL) treated with 6MP. Two of 3 adult patients with very high TGN concentrations and ...
Genotype-Phenotype Correlations OMIM Alves et al. (1999) analyzed 24 children who received curative therapy of ALL with thiopurine drugs. Four of them were shown to be heterozygous for the TPMT*3A allele; all 4 patients exhibited signs of severe hepatic toxicity during ...
Molecular genetics OMIM In a patient with TPMT deficiency reported by Evans et al. (1991), Krynetski et al. (1995) identified a mutation in the TPMT gene (187680.0001). The mutation was heterozygous in both the proposita and her mother and absent in ...