The success of neonatal screening beyond war: a case report of purine nucleoside phosphorylase deficiency

We describe the case of a newborn affected by purine nucleoside phosphorylase (PNP) deficiency, diagnosed through newborn screening during the war in Ukraine; on the basis of this experience, it was possible to verify retrospectively the performance of the Tuscan protocol on mass spectrometry (MS/MS) for severe combined immunodeficiencies (SCID). Amid the ongoing conflict, a Ukrainian male newborn received newborn screening on dried blood spot (DBS) on day 2, showing remarkably reduced T-cell receptor and kappa-deleting recombination excision circles (TREC/KREC) in real-time PCR. Retesting was delayed due to difficult communication with the family, and was finally performed on day 15, confirming the profile. Whole exome sequencing on a new DBS (on day 20) indicated an extremely rare SCID - PNP deficiency. The newborn was candidate for allogeneic hematopoietic stem cell transplantation (HSCT) - the only curative treatment, a complex procedure still ongoing in Ukraine despite the war. However, the family preferred to seek medical care in Germany. As part of a collaborative initiative with the Meyer Children Hospital IRCCS (Florence), the biochemical profile was confirmed pre-HSCT by quantifying four PNP biomarkers by MS/MS. Given the rareness of PNP deficiency, these biomarkers were measured also in the three DBSs collected on day 2, 15 and 20, according to the MS/MS-based Tuscan protocol for newborn screening of SCID, as an additional confirmation of its performance. HSCT was successfully performed in Germany at 6 months, as confirmed also by the monitoring of PNP biomarkers by MS/MS. This case highlights the importance of sustaining preventive healthcare services, and of promoting cross-border partnerships, especially in times of crisis.