Improving self-collected dried blood spot specimens for phenylketonuria monitoring: a 10-year computer vision review of dried blood spot specimen quality

Background

Biochemical monitoring of phenylketonuria (PKU) is performed using dried blood spot (DBS) specimens, usually collected by the patient or carer. DBS quality affects DBS phenylalanine results and self-collected specimen quality may often be sub-optimal. However, it is unclear how often specimen quality affects clinical interpretation of PKU monitoring results, or whether sustained improvements in DBS quality are achievable in this setting.

Methods

We used a computer vision algorithm to objectively assess DBS quality in 8472 DBS specimens collected from 111 PKU patients over a 10-year period. Trends in specimen quality were analysed over time, by patient, and by frequency of specimen collection. We modelled the effect of sub-optimal DBS size on phenylalanine result classification against European PKU treatment guidelines.

Results

The proportion of poor-quality DBS decreased from 66.5 % to 3.2 % over a 10-year period. The median proportion of acceptable specimens returned by each patient each year improved from 28.6 % in 2015/16 to 100 %. Patients returning specimens more frequently showed better DBS quality performance, with acceptability rates of 96.3 % in patients who returned ≥10 specimens in 2024–25, compared to 78.3 % in patients who returned <5 specimens. Improvement in DBS quality reduced potential misclassification against PKU treatment guidelines due to DBS size from 3.1 % to 0.6 %.

Conclusions

Without training and education, DBS quality in self-collected specimens may be very poor. However, substantial improvements are achievable for PKU monitoring specimens, reducing total measurement error and the risk of incorrect clinical interpretation of results.