Test for Sanfilippo Syndrome Type A Shows Promise for Screening Newborns

Test for Sanfilippo Syndrome Type A Shows Promise for Screening Newborns

A new test that uses dried blood spots has been developed for diagnosing Sanfilippo syndrome type A. This test would prove especially useful for disease screening in newborns, according to a study.

The study, “Detection of Mucopolysaccharidosis III-A (Sanfilippo Syndrome-A) in Dried Blood Spots (DBS) by Tandem Mass Spectrometry,” was published in Molecular Genetics and Metabolism.

The only rapid diagnostic test currently available for Sanfilippo syndrome Type A requires the extraction of white blood cells or fibroblast cells from patients. The test is able to detect the activity of the enzyme sulfamidase, which is defective in Sanfilippo patients, through a modified form of its subststrate (the substance on which the enzyme normally works).

Researchers developed a diagnostic test capable of detecting defects in enzyme activity in dried blood spots; it is particularly suitable for screening newborns for the disease.

After screening for a series of synthetic substrates, the one with more sensitivity and specificity to sulfamidase was chosen. The synthetic substrate was able to detect sulfamidase activity in dried blood spots from a healthy individual, where it showed a high degree of sensitivity and specificity.

The test also was effective when used on blood samples that had been frozen or stored at very low temperatures for 68 days. This indicates there would be minimal loss in the detection of enzyme activity during sample storage and shipping.

After optimizing the test and its conditions, researchers tested it on samples that were known to be defective in sulfamidase. The test could easily detect the difference in sulfamidase activity in samples from normal mice compared with mice lacking the gene for sulfamidase.

The next step was to apply the test on human-derived samples. The test was used to assess sulfamidase activity using dried blood samples from 238 healthy newborns and eight patients with Sanfilippo syndrome.

Healthy newborns had a mean enzyme activity of 0.3 μmol/L/h (within a range of 0.1-0.81 μmol/L/h), while seven of the eight patients had an enzyme activity below 0.02 μmol/L/h and one patient had an enzyme activity of 0.056 μmol/L/h.

In laymens’ terms, those values reveal that the newly developed assay could effectively differentiate between normal and patient samples.

According to researchers, this newly developed test is “appropriate for high-throughput NBS [Newborn Screening & Genetics] laboratories and reference laboratories.” The researchers also stated they “plan to initiate pilot studies using the new sulfamidase assay in a NBS lab to explore the robustness of the assay and the number of false positives.”

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