ADA-SCID testing can be incorporated in routine neonatal screening

ADA-SCID testing can be incorporated in routine neonatal screening

Published Date: 22/2/17

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medwireNews: An Italian research team has developed an analytical method that enables the inclusion of adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) testing in a tandem mass spectrometry-based newborn screening programme.

They also generated a second-tier test to help reduce the number of false–positive results.

Thus far, the pilot programme has identified one infant with ADA-SCID, the researchers report in the Journal of Pharmaceutical and Biomedical Analysis.

The method allows the extraction of 2-deoxyadenosine (dAdo) and adenosine (Ado) – metabolites that accumulate in the absence of the ADA enzyme – from dried blood spots routinely collected at birth. And the technique does not preclude the extraction of other metabolites tested during routine screening, such as succinylacetone, amino acids and acylcarnitines.

Reference values for dAdo and Ado levels were established by applying the method to 50,000 infants born between 2011 and 2012, with an upper limit of 0.09 μmol/L and 1.61 μmol/L, respectively, signifying normal concentrations.

When applied to samples from four children known to have early-onset ADA-SCID and five with delayed-onset disease, the test showed higher than normal levels of dAdo and Ado, thus confirming the effectiveness of the approach, say Giancarlo la Marca (Meyer University Children’s Hospital, Florence, Italy) and colleagues.

In light of some false–positive results, they developed a second-tier test, for which the reference values were established using samples from 250 newborns, with concentrations below 0.1 μmol/L and 0.1–2.0 μmol/L indicating normality of dAdo and Ado, respectively.

The second-tier test correctly detected higher than normal ADA metabolite levels in the samples from the nine ADA-SCID patients.

During the first 18 months of the pilot programme, 10 samples were found to have abnormal dAdo levels in the initial screen, the study authors report. Of these, nine were shown to be false–positives by the second-tier test, whereas one presented values out of the normal range. A second dried blood spot from this infant confirmed the presence of high levels of ADA metabolites, and further molecular and biochemical analysis established a diagnosis of ADA-SCID.

la Marca et al write: “The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program.”

They point out that “[e]arly diagnosis of SCID allows treating the affected patients very soon so avoiding severe complications due to infectious disease which are always expected in the follow-up of immunodeficient patients.”

© 2017 Springer Healthcare Ltd

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