After 92 years, since the discovery of A-T, our study seems to be the first study to explore the various concerns and anguishes A-T parents face before diagnosis and the impact of delayed diagnosis by answering a semi-structured questionnaire. NBS for SCID unexpectedly creates an opportunity for a very early A-T diagnosis. The benefits for SCID are clear: preventing severe infections by treatment with an early stem cell transplant, which improves life expectancy in this group . Although this is a major argument to implement NBS for SCID, the benefits for the outcome of A-T patients are less clear. What started as a questionnaire to investigate parents’ opinion about a current discussion in the Netherlands gave us an insight in parents’ experience with A-T. Many parents had experienced uncertainty towards the diagnosis, having the feeling that their child is ill and that medical teams are not recognizing this. In these cases, the diagnosis meant a form of relief. Also, parents experienced that their child had been subjected to unnecessary potentially dangerous procedures, e.g., radiation as patients with A-T have an increased radiosensitivity. On the other hand, some parents who only had mild medical issues with their “clumsy” child had experienced the joy of seeing a (seemingly) healthy child grow up (also known as the “golden year(s)”).
The knowledge of having a child with a genetic disease is important for parents. Many of them are young families with an ongoing child wish; others have a completed family but would have decided otherwise if they knew the diagnosis A-T at that time.
In contrast to our expectations, A-T parents were divided about the loss of golden year(s). We expected that there was at least a loss of potential golden year(s) for all parents (also for those who favored an early diagnosis). In this questionnaire, many parents commented on the insecurity before diagnosis and the relief of the eventual diagnosis. These comments have emphasized the impact of not having a diagnosis. Also, parents confirm the importance that there is an advantage for heterozygous ATM carriers as the increased risk for breast cancer requires early screening .
In the first statement, 19/35 parents would have preferred a diagnosis shortly after birth and 9/35 parents preferred not to hear the diagnosis at that time. As A-T is a devastating diagnosis that no parent ever wants to hear, it is most likely a negative memory which can influence a parent’s opinion in this question. In the final question, we gave parents the opportunity to make a final choice taking all the advantages and disadvantages in their specific situation into consideration. The answer was based on parents’ personal perspectives as parents could not decide for the entire group. We can imagine that parents would choose differently when they would have to make a decision for the whole group, instead of their specific personal situation, considering the complexity of this dilemma.
So far, limited studies show the percentages of A-T newborns that can be diagnosed as a result of NBS by retrospective analysis of NBS of Guthrie cards. At first, a Californian group investigated the records of an A-T cohort over 25 years. Seven samples had low TREC levels in a cohort of 13 A-T patients (54%) . In a small Swedish study, all four patients showed reduced numbers of TRECs. In the Dutch A-T cohort, we tested five Guthrie cards and four had low TRECs (unpublished data). Altogether, these data suggest that the majority of A-T patients will present with low TREC levels at birth and can possibly be diagnosed with A-T as a result of SCID screening. In the questionnaire presented to the A-T parents, no exact numbers were mentioned as these are limited data.
A-T is a very rare disease with unique features. However, similar dilemmas about NBS have been discussed for other diseases, such as Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). For these disorders, studies similar to the present one that we have performed for A-T showed a strong wish of parents (majority up to 95.9%) to implement DMD and SMA in neonatal screening programs without any therapeutic consequences at the time of the study . In the 1980s, when the screening for DMD was first discussed, a similar retrospective study was performed to objectify parents’ opinion on neonatal screening: a similar percentage of parents (75%) was in favor of an early diagnosis, based on the same arguments as diagnostic delay, practical advantages, family planning, and emotional advantages . In semi-structured interviews, parents reflected on the (delayed) diagnostic process and emphasized their feelings of worry and anxiousness of having an undiagnosed ill child and the eventual relief of being guided by a dedicated DMD team . In all these aspects, our study shows similarities to the studies about screening for this untreatable disorder.
At this moment, a curative treatment for A-T is not available. NBS may identify pre-symptomatic patients, while—on the contrary—recent studies have also identified patients at the highest risk for early morbidity and mortality . Whenever a form of treatment becomes available, these groups at both ends of the clinical spectrum may be the first to benefit from early medical intervention. Undoubtedly, new technologic developments will influence the discussion about NBS for A-T.
This study has some limitations: it is a relatively short questionnaire in a small cohort. With only little number of cases, no subgroup analysis was possible. Despite the limitations, however, we feel it is valuable to share the opinion of our cohort of A-T parents. Future research should address structured interviews with A-T parents. In addition, non-A-T parents should be introduced in this subject and asked for their opinion as well. This way, the current health policy regarding SCID screening in the Netherlands could be re-evaluated taking (A-T) parents’ perspectives into consideration.