Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening.

Andrea Martín-Nalda,Judit García-Villoria,Alba Parra-Martínez,Laura Alonso,Marina García-Prat,Pere Soler-Palacín,Jacques G Rivière,Ana Argudo-Ramírez,Mónica Martínez-Gallo,Jose Luis Marín-Soria,Roger Colobran,Jose Antonio Arranz-Amo,Giancarlo La Marca,Mireia Català-Besa

doi:10.3390/ijns7040062

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP deficiency was detected by TREC analysis.

Highlights

Severe combined immunodeficiency (SCID) is the most severe T-cell immunodeficiency, exposing children to immune dysregulation and recurrent opportunistic infections
Among the accumulated experience of newborn screening (NBS) for several metabolic and other inherited diseases in Europe and worldwide [3], NBS for SCID was first implemented in Wisconsin in 2008 and was subsequently adopted in several geographic areas, including Catalonia (Spain) in 2017 [1,2,4]
A hallmark feature for the diagnosis of the disease is the accumulation of the substrate metabolites in plasma and/or urine. The increases in these metabolites can be detected in dried blood spot testing by tandem mass spectrometry (TMS) used for newborn screening [8]

Summary

Background

Severe combined immunodeficiency (SCID) is the most severe T-cell immunodeficiency, exposing children to immune dysregulation and recurrent opportunistic infections. Purine nucleoside phosphorylase (PNP) deficiency is a rare combined autosomal recessive primary immunodeficiency with associated non-immune features that accounts for approximately 4% of all SCID cases. It is characterized by progressive T-cell immunodeficiency and variable abnormalities of humoral immunity, with autoimmunity, malignancy, and neurological impairment [5,6]. A hallmark feature for the diagnosis of the disease is the accumulation of the substrate metabolites (dIno, Ino, dGuo, and Guo) in plasma and/or urine The increases in these metabolites can be detected in dried blood spot testing by tandem mass spectrometry (TMS) used for newborn screening [8]. Detection of a defect in the PNP gene helps to confirm the diagnosis and enables genetic counselling [6]

Case Presentation

Month Old

Findings

Discussion