Early vs. delayed diagnosis of severe combined immunodeficiency: a family perspective survey

Abstract

Infants affected with severe combined immunodeficiency (SCID) are susceptible to severe and recurrent infections and do not survive unless provided with immune reconstituting treatments. In the absence of population-based newborn screening, infants with SCID who do not have an affected older relative are ascertained only after they have developed infections. However, only limited data are available from the perspective of patients and families to indicate what proportion of SCID cases might benefit from earlier detection by pre-symptomatic screening, whether adequate treatment facilities are available, and how screening could improve SCID treatment outcomes. A survey of parents of children with SCID evaluated family history, pre- and post-diagnosis events, outcomes, and impact of SCID on families. Affected infants diagnosed with SCID as neonates had better survival, demonstrating the potential benefit of universal newborn screening.

Figure 1

Flow diagram of surveyed patients. This diagram shows the excluded cases, number of families with more than one affected members, and percentage of cases derived from families with 1, 2, or 3 affected members.

Figure 2

Composition of mortality in SCID patients surveyed. Of the 61 deaths, Not Diagnosed were cases of SCID not diagnosed pre-mortem (dark gray); diagnosed cases were separated into those who received (white) and those who did not receive (light gray) transplantation or enzyme replacement.

Figure 3

Survival of treated SCID patients. (A) Patients grouped by birth year. All treated patients, solid line (81.4%, n=93); born pre-1995, dashed/dotted line (78.6%, n=28); born 1995–1999 dashed, (75%, n=24); born in 2000 or later, with no difference pre or post 2004, dotted (87.2%, n=41). (B) Patients grouped by treatment type (includes only patients reporting a single treatment, since the order of different treatments was not available); HLA matched sibling HSCT, long-dashed line (93%, n=16); haploidentical T-depleted parent HSCT, short dashed (84%, n=50); adult matched unrelated HSCT, dotted (67%, n=9); matched unrelated cord blood, solid (67%, n=9); and PEG-ADA dashed/dotted (80%, n=5).

Figure 4

Percentage of families citing particular reasons for not receiving definitive therapy among patients who were diagnosed with SCID, but died without being treated (n = 14).

Figure 5

Age at definitive treatment for SCID by mortality. Living (white) and deceased (gray) patient numbers are compared (p=0.038).

Figure 6

Comparison of infant mortality between those groups of neonates who were not tested (n= 138, left) and tested (n= 20, right) for SCID. Testing was performed only if an affected relative’s SCID diagnosis had made parents and medical providers aware of the risk. Proportion of deceased infants is shaded in each pie chart.