Non-invasive Urine Test May Help in AADC Deficiency Diagnosis, Case Report Says

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by David Melamed |

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A case study of a 3-month-old patient provided evidence to support the use of a urine organic acid analysis in the diagnosis of aromatic l-amino acid decarboxylase (AADC) deficiency, offering a non-invasive approach for identifying the disease.

The report, “Urine Organic Acid (UOA) Analysis for the diagnosis of Aromatic L-Amino Acid Decarboxylase (AADC) deficiency,” was published in the journal Pathology.

AADC deficiency is a rare genetic disease caused by mutations in the DDC gene, which provides instructions for making the AADC protein. This protein plays a vital role in the synthesis of two neurotransmitters, dopamine and serotonin, that are important for nervous system activity.

One common method used to diagnose AADC deficiency is to measure the levels of neurotransmitters and other metabolites in the cerebrospinal fluid (CSF), the clear liquid that surrounds and protects the brain and spinal cord.

Collection of CSF, however, requires an invasive procedure called lumbar puncture, also known as a spinal tap. There are several risks associated with a lumbar puncture and the procedure itself is technically challenging.

Evidence has suggested that a non-invasive test measuring the levels of organic acids in urine could be used as a diagnostic tool for AADC deficiency. This is because organic acids are involved in the metabolic pathways used to synthesize neurotransmitters, and changes in organic acid levels can be detected in urinalysis.

Two organic acids in particular, vanillactic acid and N-acetyl-vanilalanine, are observed at higher levels in patients with AADC deficiency.

In the case study, a 3-month-old infant presented with symptoms including upper limb spasm and abnormal eye movement.

To detect any metabolic abnormalities, clinicians ordered a urine organic acid analysis, which showed high levels of vanillactic acid and N-acetyl-vanilalanine. As these findings were indicative of AADC deficiency, a CSF analysis was performed and revealed characteristics indicative of AADC deficiency based on the patient’s CSF neurotransmitter profile.

A genetic analysis confirmed the diagnosis by identifying a specific mutation in the patient’s DDC gene.

Based on the results, the team believes that urine organic acid analysis has the potential to replace the current CSF analysis method.

“Our case illustrates the potential of using non-invasive UOA [urine organic acid] to replace CSF neurotransmitter for the diagnosis of AADC,” the researchers wrote. “This is particularly useful clinically if sampling of CSF is practically infeasible.”

This case study abstract was scheduled to be presented at the Pathology Update 2020 conference, March 20–22, 2020 in Sydney, Australia, but the conference was cancelled due to the COVID-19 pandemic.