Blood Spot Assay Validated for Enzyme Deficiency Disease

A reference interval value to IDUA activity using a DBS assay has been evaluated as to whether this assay could be an efficient tool to diagnose patients with mucopolysaccharidosis type I (MPS I) disease.

Scientists at the Federal University of São Paulo (Brazil) collected blood samples from 164 Brazilian healthy volunteers (HV) from both genders, 69 men and 95 women, age range from 18 to 73 years, who did not show any clinical evidence of chronic disease and/or other genetic disease. The validation group (VG) comprised DBS and leukocyte samples from 36 individuals clinically suspected of MPS I, sent by physicians from 12 different Brazilian States. Cutoff values initially used to discriminate HV from MPS I patients were 1.1 µmol/L/hour and 0.02 nmol/mg protein/hour for DBS and leukocyte assays, respectively.

The IDUA activity range on HV DBS samples were 1.40 µmol/L/hour to 7.78 µmol/L/hour. In the VG test group, 11 of the 36 individuals clinically suspected of MPS I had the diagnosis confirmed by DBS and a reference leukocyte assay. A new proposed cutoff value of 1.5 µmol/L/hour had the sensitivity, specificity, and predictive values of 100%. The authors suggest that the interpretation of IDUA activity results should be performed according to the following criteria: for activity results lower than 1.2 µmol/L/hour, the DBS method is an accurate tool to diagnose MPS I, together with the evaluation of clinical symptoms and other laboratory results; for activity results between 1.2 µmol/L/hour and 1.8 µmol/L/hour, another diagnostic assay should be performed in leukocyte, plasma, or fibroblast samples to confirm these suggestive results; and for activity results higher than 1.8 µmol/L/hour, the DBS assay is reliable and safe to exclude the diagnosis of MPS I.

Mucopolysaccharidosis type I, also known as Hurler Syndrome, is caused by a deficiency of the enzyme α-L-iduronidase that leads to the accumulation of glycosaminoglycans, such as heparan sulfate, in lysosomes. MPS I patients present a spectrum ranging from a severe to an attenuated phenotype. The authors concluded that the determination of IDUA activity using a DBS assay is an accurate 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 sample. The article was published online on July 22, 2011, in the Journal of Clinical Laboratory Analysis.

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