Scientists Test New Method That Can Help Diagnose AADC Deficiency

Technology may boost accuracy of diagnosis by preventing possible false results

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Scientists have discovered a new technique to measure the activity of the aromatic-L-amino acid decarboxylase (AADC) enzyme to help diagnose AADC deficiency.

The assay, which uses liquid chromatography-tandem mass spectrometry, was detailed in a study, “Biochemical diagnosis of aromatic-L-amino acid decarboxylase deficiency (AADCD) by assay of AADC activity in plasma using liquid chromatography/tandem mass spectrometry,” published in Molecular Genetics and Metabolism Reports.

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AADC deficiency is characterized by diminished activity of the AADC enzyme, which helps to make dopamine and serotonin, signaling molecules (neurotransmitters) that are essential for many aspects of brain activity. As new treatments like gene therapies are being developed, there is renewed interest in finding methods to detect AADC deficiency, since many cases remain undiagnosed and early treatment is likely to yield better outcomes.

Here, a team of scientists in Brazil devised a novel method to diagnose AADC deficiency. Simply, the method involves first mixing a small blood sample from a patient with an amount of L-dopa, the “raw material” that the AADC enzyme uses to create dopamine. After incubating for about 90 minutes, the amount of dopamine that is generated is measured using a technique called liquid chromatography-tandem mass spectrometry, or LC-MS/MS.

LC-MS/MS is a tool for identifying molecules that combines two techniques: liquid chromatography, which involves analyzing how molecules move through different liquids, and mass spectrometry, which analyzes molecules using electric and magnetic fields.

“To our knowledge, there are no reports in the [published scientific literature] concerning the quantification of AADC activity using LC-MS/MS to measure the final product of the reaction,” the scientists wrote.

They noted that high-performance liquid chromatography (HPLC) has been used in similar assays to measure AADC activity by detecting dopamine produced by the enzyme.

“When compared with the original HPLC-based enzyme assays, the use of LC-MS/MS is highly recommended since this technology improves the correct identification and quantification of the reaction products, preventing possible false positive or negative results,” the researchers wrote.

The team also noted that LC-MS/MS can be more easily adapted to measure other related molecules, since they can be measured in the same assay by adding additional parameters to the analytical program.

As a proof-of-concept, the scientists used their LC-MS/MS-based assay to measure AADC activity in seven people with known AADC deficiency, and in 35 people without the disease (controls). All of the patients had no detectable enzyme activity, whereas enzyme activity was readily detectable for controls (average 32.66 nanomoles/min/L).

“The data obtained showed clear discrimination between confirmed [AADC deficiency] patients and healthy controls,” the researchers wrote.

They proposed that this novel method could be used to test for AADC deficiency, due to clinical suspicion or as a confirmatory test after newborn screening.