ITPA encodes inosine triphosphate pyrophosphohydrolase (ITPase), a protective enzyme that hydrolyzes non-canonical purine nucleotides including inosine triphosphate (ITP), deoxyinosine triphosphate (dITP), and xanthosine triphosphate (XTP) to their monophosphate derivatives 1. This pyrophosphatase activity serves as a cellular surveillance mechanism to exclude non-canonical purines from nucleotide pools, preventing their incorporation into RNA and DNA and avoiding chr20 lesions 1. ITPA deficiency is associated with severe disease manifestations. Complete ITPA deficiency causes early infantile epileptic encephalopathy characterized by progressive neurodegeneration, microcephaly, developmental delay, and seizures, with most patients dying before 4 years of age 2. Neuroimaging reveals T2-signal abnormalities and diffusion restriction in white matter tracts, particularly the posterior limb of internal capsule 2. ITPA polymorphisms affect approximately one-third of the human population and have significant clinical implications 3. The Pro32Thr variant (rs1127354) causes varying degrees of ITPA deficiency and influences drug responses 1. These polymorphisms increase risk of ribavirin-induced hemolytic anemia in hepatitis C patients 4 and thiopurine-related adverse effects including neutropenia 5, making ITPA genotyping valuable for personalized therapy decisions.