Alternative titles; symbols
SNOMEDCT: 238011005;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20p13 | [Inosine triphosphatase deficiency] | 613850 | 3 | ITPA | 147520 |
A number sign (#) is used with this entry because inosine triphosphatase deficiency is caused by heterozygous, homozygous, or compound heterozygous mutation in the ITPA gene (147520) on chromosome 20p13.
Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes (Sumi et al., 2002).
Vanderheiden (1969) found relatively high levels of inosine triphosphate in the red cells of 2 sibs and suggested that this resulted from deficiency of inosine triphosphatase activity. In a follow-up study, a high level of ITP was found in 7 of over 6,000 samples from mainly unrelated persons. Persons with very low enzyme levels were apparently homozygous. The enzyme is a cytosolic nucleoside triphosphate pyrophosphohydrolase specific for ITP (Vanderheiden, 1975).
ITPase deficiency is not associated with any defined pathology other than the characteristic and abnormal accumulation of ITP in red blood cells. Nevertheless, ITPase deficiency may have pharmacogenomic implications, and the abnormal metabolism of 6-mercaptopurine in ITPase-deficient patients may lead to thiopurine drug toxicity (Fraser et al., 1975; Sumi et al., 2002).
Greene (1986) stated that the Camden Cell Bank has lymphoblastoid cells and skin fibroblasts supplied by Vanderheiden from a 29-year-old woman (GM1619) with ITPase deficiency. The lymphoblastoid cells had only 20% normal ITPA activity after recovery from storage in liquid nitrogen. The possibility that ITP deficiency has some clinical significance, perhaps under conditions of stress, should be considered.
The frequency of heterozygosity for ITPase deficiency in Caucasian populations is estimated to be 5 per 100 (Fraser et al., 1975; Sumi et al., 2002).
Sumi et al. (2002) identified 2 mutations in the ITPA gene (147520.0001-147520.0002) associated with deficient ITPase enzyme activity.
Fraser, J. H., Meyers, H., Henderson, J. F., Brox, L. W., McCoy, E. E. Individual variation in inosine triphosphate accumulation in human erythrocytes. Clin. Biochem. 8: 353-364, 1975. [PubMed: 1204209] [Full Text: https://doi.org/10.1016/s0009-9120(75)93685-1]
Greene, A. E. Personal Communication. Camden, N. J. 3/4/1986.
Sumi, S., Marinaki, A. M., Arenas, M., Fairbanks, L., Shobowale-Bakre, M., Rees, D. C., Thein, S. L., Ansari, A., Sanderson, J., De Abreu, R. A., Simmonds, H. A., Duley, J. A. Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. Hum. Genet. 111: 360-367, 2002. [PubMed: 12384777] [Full Text: https://doi.org/10.1007/s00439-002-0798-z]
Vanderheiden, B. S. ITP pyrophosphohydrolase and IDP phosphohydrolase in rat tissue. J. Cell. Physiol. 86: 167-176, 1975. [PubMed: 170291] [Full Text: https://doi.org/10.1002/jcp.1040860118]
Vanderheiden, B. S. Genetic studies of human erythrocyte inosine triphosphatase. Biochem. Genet. 3: 289-297, 1969. [PubMed: 4376397] [Full Text: https://doi.org/10.1007/BF00521144]