Purine nucleoside phosphorylase (PNP) deficiency: across-the-board severe combined immunodeficiency

Purine nucleoside phosphorylase (PNP) deficiency is a rare, autosomal recessive, inborn error of immunity. It is characterized by progressive immune abnormalities ranging from severe combined immunodeficiency (SCID) to combined immunodeficiency less profound than SCID, neurological abnormalities and autoimmunity. Early detection and diagnosis before the development of life-threatening complications are crucial.

Immune cell subsets were assessed by flow cytometry, serum immunoglobulins and uric acid levels were evaluated, and genetic testing was performed for all patients.

Herein, we present six Egyptian PNP deficiency patients from four different families. We describe the patients’ clinical phenotypes, their immunological profile as well as their genetic results. Sequence analysis results detected 4 different variants in the PNP gene; 1 likely pathogenic frameshift deletion c.452del; p.Asn151MetfsTer20 was found in one family, 1 pathogenic nonsense variant c.172C > T; p.Arg58Ter, and 2 likely pathogenic missense variants c.682G > C; p.Ala228Pro and c.722T > C; pIle2241Thr.

In conclusion, PNP deficiency is a variable immunodeficiency and should be considered in various clinical contexts, with or without neurological manifestations. Hematopoietic stem cell transplantation offers a good treatment option, with excellent clinical outcomes, when performed in a timely manner.