Evaluation of α-iduronidase in dried blood spots is an accurate tool for mucopolysaccharidosis I diagnosis

Abstract

Mucopolysaccharidosis type I (MPS I) is caused by a deficiency of the α-L-iduronidase (IDUA), which leads to the accumulation of glycosaminoglycans in lysosomes. MPS I patients present a spectrum ranging from a severe to an attenuated phenotype. Once clinical suspicion is present, diagnosis of MPS I can be performed by enzyme activity determination and/or molecular analysis. The aim of this study was to establish a reference interval value to IDUA activity using a dried blood spots (DBS) assay and to evaluate whether this assay could be a secure tool to diagnose MPS I patients. IDUA activity range on HV DBS samples were 1.40-7.78 µmol/l blood/hr. Regarding the validation group, 11 of the 36 individuals clinically suspected of MPS I had the diagnosis confirmed by DBS and reference assay (leukocytes). When we considered the new proposed cutoff value of 1.5 µmol/l blood/hr, the sensitivity, specificity, and predictive values were 100%. Our results strongly suggest that the determination of IDUA activity using a DBS assay is a secure tool for MPS I diagnosis. However, it is extremely important to assure that all recommendations for collection, transport, and storage are correctly followed to guarantee the quality of the samples.