Lisi, Emily C.

AbstractPompe disease (PD) is an autosomal recessive lysosomal storage disorder causing progressive glycogen accumulation in muscles, with variability in age of onset and severity. For infantile‐onset PD (IOPD), initiation of early treatment can be life‐saving; however, current newborn screening (NBS) technology cannot distinguish IOPD from late‐onset PD (LOPD) without clinical workup. Therefore, families of LOPD infants diagnosed by NBS may now spend years or even decades aware of their illness before symptoms appear, creating a pre‐symptomatic awareness phase with which the medical community has little experience. The present study examines the effects of receiving a positive NBS result for PD on families. In‐depth qualitative interviews were conducted with mothers of nine children (three IOPD and six LOPD) diagnosed via NBS, exploring their experiences, understanding of PD, how they are coping, and what impact diagnosis is having on family life. Interviews were coded using MaxQDA v.12 and analyzed for thematic trends. While overall opinion of NBS was favorable, it is clear many of the concerns anticipated by HCPs, patients, and families regarding NBS for late‐onset LSDs are being realized to varying degrees; LOPD families are becoming patients‐in‐waiting. Increased fear/anxiety and living with uncertainty (regarding diagnosis, their children's future, and when to start treatment) were predominant themes, with all families voicing considerable emotional reactions and varied social and healthcare support concerns. Coping strategies and psychosocial challenges are interpreted using Rolland & Williams’ Family Systems Genetic Illness model. Recommendations for improvement in delivery of service, as well as families’ advice for future parents and HCPs, are discussed.

AbstractThe clinical significance of the c.427G>A (p.A143T) variant in GLA is a topic of debate within the lysosomal storage disease community. A review of the literature and published case reports found the clinical impact of the variant to range from classic Fabry symptoms to healthy unaffected males with normal alpha‐ galactosidase enzyme levels, leaving clinicians unsure of how to manage these individuals. As the number of states testing for Fabry disease on their newborn screening panel has increased, more people with this variant are being identified. The goal of this project was to learn how the uncertainty surrounding the clinical significance of the p.A143T variant affects those with this change. A self‐response questionnaire was developed to explore this topic. In addition to evaluating participant feelings, the questionnaire explored individuals’ beliefs regarding the pathogenicity of the variant. Results suggest that people have diverse feelings regarding reclassification of the p.A143T variant. Around half of those surveyed reported feeling frustrated by the lack of clear information. Despite the ambiguity regarding the health consequences of this variant, many participants felt that knowing this result helps guide medical management.