Cross correction following haemopoietic stem cell transplant for purine nucleoside phosphorylase deficiency: Engrafted donor-derived white blood cells provide enzyme to residual enzyme-deficient recipient cells

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is an immunodeficiency disorder characterized by recurrent infections, failure to thrive and neurologic symptomatology. While enzyme replacement therapy (ERT) is a therapeutic option for adenine deaminase (ADA) deficiency, a similar disorder, this is not available for PNP deficiency, and bone marrow transplant (BMT) is the only treatment option. Moreover, even with BMT, improvement of neurological deficits is not definite. We describe a 16-month-old boy who underwent BMT for PNP deficiency which resulted not only in freedom from infections but also in neurological improvement and autologous T-cell recovery. Pre-transplant, this child had severe lymphopenia with recurrent infections and psychomotor retardation. Post-transplant, in the presence of mixed chimerism, he had normal lymphocyte count, including presence of recipient T cells and neurological improvement. The re-emergence of recipient T cells, when there were virtually no such cells pre-transplant, and the neurological improvement are indicative of improvement of the enzyme deficiency in tissues which remain genetically enzyme depleted. These defects are not directly corrected by BMT, but are due to delivery of the missing enzyme by the transplanted tissue. In this aspect, transplantation in PNP deficiency is similar to transplantation in other inborn errors of metabolism where the engrafted donor cells deliver enzyme and restore function to deficient tissues. This further lends support to the recommendations that BMT should be the favoured treatment option in disorders like ADA deficiency or Hurler syndrome, where, even though ERT is available, it is limited by inability to correct the central nervous system defects.