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Inosine triphosphatase deficiency

From SNPedia

Inosine triphosphatase deficiency, also known as Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency, is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in red blood cells. [1]
The ITPA gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. [2]
Mutations in Rs1127354 and Rs7270101 can cause alterations in ITPase activity

[PMID 12384777OA-icon.png] Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency:
In patients with ITPase deficiency, it was found that found a 94C>A transversion of the ITPA gene resulted in a P32T substitution. All individuals homozygous for the 94C>A mutation had completely deficient erythrocyte ITPase activity, accompanied by the abnormal accumulation of ITP and red blood cells. ITPase activity was decreased in all heterozygotes, with a mean ITPase activity of 22.5% of the control value, consistent with a dimeric structure of ITPase. In heterozygotes, only 1 of the 4 possible dimers would be composed of wildtype subunits.
In the same study patients with ITPase deficiency also had an SNP in intron 2, IVS2+21A>C. ITPase activity of heterozygotes was 60% that of the normal control mean.

In individuals who were compound heterozygous for Rs7270101 and Rs1127354 mutations ITPase activity was 10% of the normal control mean.