Cross-sectional audit assessing the quality of dried bloodspot specimens received by UK metabolic biochemistry laboratories for the biochemical monitoring of individuals with Phenylketonuria

BACKGROUND: Sapropterin has been approved as a treatment option for individuals with Phenylketonuria in the United Kingdom. Individuals are assessed as responsive to Sapropterin by a ≥30% reduction in Phenylalanine (Phe) concentrations using dried blood spot (DBS) specimens. DBS quality is critical for accurate and precise measurement of Phe. Currently, UK national guidelines for DBS specimen acceptance do not exist for patient-collected DBS specimens. We adopted evidence-based guidelines for specimen acceptance criteria and retrospectively assessed the impact of introducing these guidelines on specimen rejection rates. Methods: Laboratories were invited to audit the quality of DBS specimens routinely received for Phe monitoring using: (1) existing acceptance/rejection criteria and (2) proposed national guidelines. RESULTS: = 299); 211/299 (70.6%) of DBS specimens were too small or multi-spotted. 380 individuals had more than one sample evaluated; 231/380 (60.8%) provided specimens of acceptable quality, 37/380 (9.7%) consistently provided poor-quality DBS specimens. CONCLUSIONS: There is significant variability in the quality of patient-collected DBS specimens. If unacceptable specimens are not rejected, imprecise/inaccurate results will be used in clinical decision making. Using annual workload data for England, this equates to 12,410 incorrect results. Individuals and parents/carers should receive ongoing training in blood collection technique to ensure use of evidence-based acceptability criteria does not cause undue distress from increased sample rejection rates.