Q&A: Expanded rollout of adenosine deaminase deficiency newborn screenings recommended
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Key takeaways:
- T-receptor excision circle screenings can miss cases of adenosine deaminase deficiency (ADA), which can be fatal.
- Tandem mass spectroscopy (TMS) screenings can be added to current procedures to identify ADA at a negligible cost.
- TMS screenings for ADA are now standard in Michigan and can be replicated elsewhere.
Tandem mass spectroscopy screenings for newborns can identify partial or delayed adenosine deaminase deficiencies, which can have potentially fatal complications, according to a review published in Annals of Allergy, Asthma & Immunology.
After examining three recent cases, Nicholas L. Hartog, MD, FAAAAI, FACAAI, an allergy and immunology specialist with Spectrum Health, and colleagues called for expanded use of these screenings due to their lifesaving results and negligible costs.
Healio spoke with Hartog to find out more about how these screenings are used and how they can be expanded.
Healio: What prompted this review?
Hartog: In Michigan, we had a planned change to start using NeoBase 2 (PerkinElmer) tandem mass spectroscopy (TMS) for another newborn screen that was rolling out. The benefit of TMS is that it enables you to run other assays in parallel with minimal to no extra cost. The NeoBase 2 kit was already validated for adenosine deaminase deficiency (ADA) screening if we chose to approve and use it.
With this transition, the state approached the State of Michigan Primary Immunodeficiency Quality Improvement Committee (PIDQIC), which is the committee responsible for primary immunodeficiency newborn screenings. The committee asked if we would like to go forward with this screen. After some discussion, we decided to proceed in rolling out this screening for newborns in Michigan.
Just prior to rolling it out, we did have a patient known to us with ADA-severe combined immunodeficiency (SCID) who was missed by the T-receptor excision circle (TREC) newborn screen aimed at detecting SCID, and this patient passed away (patient 1 in the manuscript).
Due to the uniqueness of ADA deficiency, it is known that cases of ADA-SCID can be missed in TREC screenings, and this is well documented in the literature. In addition, we knew that we would be the first state in the U.S. and really one of the first areas in the world to roll out screening for ADA deficiency. The only other area in the literature is a targeted area in Italy.
Healio: Were there any particularly surprising or significant findings in your review of these three cases?
Hartog: The significant finding was the ability to detect various forms of ADA deficiency. In addition to ADA-SCID, there are other forms of ADA deficiency of varying severity, as described in the paper. In case 2 and 3, we highlight two ends of the spectrum in severity that were both detected by the newborn screening.
Looking at the results, there is some suggestion that the ADA screening by TMS may have some genotype/phenotype predictions based on the levels of 2’-deoxyadenosine detected on the newborn screen. There will need to be more patients and more experience to make firm statements in this regard.
Also, it was a surprise that we had two abnormal screens in 206,321 live births. Currently, the prevalence of ADA deficiency is unknown, but it is thought to be quite rare. Universal screenings need to be done over longer time periods in diverse and broad patient populations to find its true prevalence, but this screening does enable us to do that. Also surprising is that in our experience and previous published experience, no false positive screens have been reported.
Healio: What do neonatal care teams need to do to incorporate these screenings into their care?
Hartog: For neonatal care teams, this will not change anything in the care of patients in the NICU or in infants who appear healthy who are followed up in their primary care office. Our newborn screening process remains the same. The state notifies responsible physicians of any abnormal newborn screenings, and these patients are further evaluated from that point. What this may change is if other states choose to include ADA screening in their newborn screen, we provide a framework of how to do so, including what worked for us.
Healio: On a policy level, what needs to be done to increase use of these screenings?
Hartog: First off is awareness that this screen can be done and produce reliable results. It is well known in the immunodeficiency community that ADA-SCID can be missed in TREC newborn screenings. We published our experience from 2 years in Michigan. More data from additional states would be needed to make firm statements. However, for policy makers in other states, this does provide an outline on how to successfully perform the screening.
One potential issue is patients with partial ADA deficiency. Currently, the natural history of partial ADA deficiency is not known, and it is not known when if ever these patients will develop significant immunodeficiency. This unknown natural course of partial ADA deficiency, additional cost of monitoring, psychological effect on patients and families and lack of guidelines on when to treat in this group will have to be considered when evaluating universal screening. This will have to be considered in the setting of missed cases of ADA-SCID. When evaluating, it should also be noted that a variety of effective treatments can be considered as well.
Healio: What is the next step in this research?
Hartog: The next steps for research will be continued surveillance of cases identified over time in Michigan and clinical outcomes of early identification. In addition, if other states roll out this screening, it would be important to collaborate and pool data to make more firm statements on the data with a diverse patient population.
Reference:
For more information:
Nicholas L. Hartog, MD, FAAAAI, FACAAI, can be reached at nicholas.hartog@spectrumhealth.org.