Screening movement disorders may aid AADC deficiency detection
International program tested 166 children, diagnosed disease in 1 child
An international program that screened more than 160 children thought to have movement disorders like cerebral palsy led to one child being diagnosed with AADC deficiency, a study reports.
The study, “REVEAL-CP: Selective Screening of Pediatric Patients for Aromatic L-Amino Acid Decarboxylase Deficiency with a Guthrie Card and In Silico Structural Modeling of One Index Case,” was published in Genetic Testing and Molecular Biomarkers.
AADC deficiency is usually marked by limited movement and difficulties communicating. The symptoms of AADC deficiency can resemble more common conditions like cerebral palsy and, since AADC deficiency is extremely rare, healthcare providers may not think to test for it. Correctly diagnosing AADC deficiency is crucial, especially now that a gene therapy is available as a disease-modifying treatment.
The disease is caused by mutations in the DDC gene, which provides instructions to make the enzyme AADC (aromatic l-amino acid decarboxylase) that makes certain signaling molecules, or neurotransmitters, in the brain, including dopamine. AADC promotes the conversion of the precursor molecule L-DOPA into dopamine. In AADC deficiency, the enzyme is absent and L-DOPA is instead turned into 3-O-methyldopa (3-OMD).
Screening for AADC deficiency
Since 3-OMD builds up to abnormally high levels in AADC deficiency, testing for the molecule can be a useful way to screen for the disease. Here, an international program in the U.S. and several European countries used 3-OMD testing to screen for AADC deficiency in 166 children who had symptoms that doctors thought resembled cerebral palsy.
The young patient in this investigation who presented with typical clinical features of AADC [deficiency] was only diagnosed after enrollment in this study
One of the children, a boy in Italy, had elevated 3-OMD. Further testing confirmed a diagnosis of AADC deficiency; the boy carried a mutation in the DDC gene that’s been previously reported to cause the disease. After the child was diagnosed, he received treatment with the AADC gene therapy Kebilidi (eladocagene exuparvovec-tneq), which is sold in Europe as Upstaza and developed by PTC Therapeutics, which sponsored the study.
“The young patient in this investigation who presented with typical clinical features of AADC [deficiency] was only diagnosed after enrollment in this study. This demonstrates the challenges clinicians in different healthcare settings face when encountering this rare disease,” the researchers wrote.
Finding only one case in 166 children tested might not seem like a lot, but considering that fewer than 1 in 100,000 people in Europe have AADC deficiency, the results actually indicate a comparably high rate of the disease among children with cerebral palsy-like disease, noted the researchers, who said the data support screening children with movement disorders to improve AADC deficiency detection.
“This study provides evidence that [routine screening of 3-OMD levels] targeted at patients with a movement disorder of unknown [cause] can assist in identifying those with AADC [deficiency] in an economic fashion and with a higher yield than in the general population,” the scientists wrote.
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