“Cross-correction” of PNP deficiency in neuronal cells after allogeneic HCT. In the recipient’s PNP-deficient neurons, the absence of functional PNP enzyme prevents the phosphorolysis of substrates such as deoxyguanosine (dGuo) into hypoxanthine, leading to accumulation of dGTP. This disrupts the cell’s metabolism and leads to the cell’s apoptosis. Excess dGuo can also exit the cell through transmembrane NT. After transplantation, excess dGuo is taken up by the donor PNP-proficient blood cell across the blood-brain barrier, following the concentration gradient of dGuo, where it can be further metabolized, eventually leading to the restoration of purine metabolism in the neuron. dGTP, deoxyguanosine triphosphate; NT, nucleoside transporters. Figure created with BioRender.com. Grunebaum E. (2025) https://app.biorender.com/illustrations/689a34dde8409e308ef5ce82.