Blood spot versus plasma chitotriosidase: a systematic clinical comparison

This study aimed to evaluate the agreement between blood spot and plasma chitotriosidase using the economic substrate 4-methylumbelliferyl-β-D-N,N',N"-triacetylchitotrioside, and to investigate the utility of the blood spot assay for the wide scale screening for lysosomal storage disorders among the clinically suspected.

Blinded blood spot samples were compared with the corresponding plasma levels in 199 children (56 with confirmed diagnoses of ten different lysosomal storage disorders, 73 normal controls and 70 pathological controls). Several performance criteria (limit of detection, linearity, within-run and day-to-day precision and sample stability) were also evaluated.

Plasma assay performed better by most criteria; however, blood spot performance was quite satisfactory. Quantitative values of the two methods can't be used interchangeably based on their 95% limits of agreement. Diagnostic sensitivity and specificity derived from ROC curves were 75.0 and 85.3% for the plasma assay and 71.4 and 79.0% for the blood spot assay, respectively. Cohen's kappa was 0.72 (95% CI: 0.616-0.821) denoting a good categorical agreement between the two methods.

The clinical use of blood spot chitotriosidase for the screening of lysosomal storage disorders can be quite practical, provided proper cut-off values are determined for each lab.