Autor:innen:
Dr. Theresa Winter | Universitätsklinikum Greifswald | Germany
Prof. Dr. Maria Gizewska | Pomorski Uniwersytet Medyczny w Szczecinie | Poland
Dr. Kasia Durda | Samodzielny Publiczny Szpital Kliniczny Nr 1 PUM | Poland
Dr. Jeanette Klein | Charité Campus Virchow-Klinikum | Germany
Dr. Oliver Blankenstein | Charité Campus Virchow-Klinikum | Germany
Dr. Mariusz Ołtarzewski | Institute for Mother and Child | Poland
Prof. Dr. Małgorzata Pac | Institute "Pomnik - Centrum Zdrowia Dziecka" | Poland
Prof. Dr. Matthias Nauck | Institut für Klinische Chemie und Laboratoriumsmedizin | Germany
Introduction:
Severe combined immune deficiencies (SCID) are a very heterogenic group of genetic disorders. They are characterized by severe deficiencies of essential immune defense T and/or B-cells which can be cured by stem cell transplantation. The incidence is approximately 1:50.000, but realistic numbers for Germany are not known. The federal joint committee (G-BA) decided to implement SCID in the regular newborn screening (NBS) panel in 2019, which leads to several new organizational challenges for screening laboratories and birth clinics.
Within the EU-funded Interreg Va project “RareScreen” (INT10), experiences with SCID NBS are obtained, which shall be shared prior the nationwide implementation.
Material and Methods:
Since October 2018, all newborns in the Interreg Va funding area (Western-Pomerania, North- Brandenburg (Germany) and West Pomerania Province (Poland)) can participate in an extended NBS which includes SCID. Out of the dried blood cards, which are uses for the regular NBS, TRECs (T-cell-receptor excision circles) and KREC (Kappa-deleting recombination excision circles) are being measured in a quantitative RT-PCR. The number of TRECs and KRECs correlates with newly developed T- and B-cells and allows information about T- and B-cell deficiencies. The project covers more than planned for the nationwide SCID NBS implementation, in which a TREC- only approach was decided by the G-BA. The participating screening laboratories Berlin and Greifswald currently send their sample to the screening laboratory in Szczecin, where the ImmunoIVD SCID kit (ImmunoIVD, Sweden) is used.
Results:
Since October 2018, samples of over 17.000 newborns were investigated in terms of SCID. Reasons for repeated analysis of the first sample were insufficient actin amplification, which runs simultaneously as an internal quality control or TREC and KREC copy numbers below the cutoff. The percentage of repetitions out of the first screening card had a range of 0.9-2.6 % between the three participating screening laboratories. The range of requested second screening card ranged from 0.05-0.5%. So far two positive SCID case can be reported.
Discussion and conclusion:
Since October 2018, the participating screening laboratories gain valuable experiences about the SCID NBS. Methodically, the SCID NBS is a challenge for the screening laboratories, since the quantitative RT-PCR is so far not used for the regular NBS. But the first months of SCID screening showed, that the used kit/method works reliable. The range of initially conspicuous SCID results of the first sample card is quite wide. Reasons are either pre-analytic errors, such as false sample taking (e.g. use of EDTA blood) or the incorrect punching of the card.
After a positive SCID screening, processing steps such as confirmation diagnosis and, if necessary, initiation of a therapy have be clarified until the nationwide introduction starts to ensure a stable treatment- and tracking procedure.